69,478 results match your criteria Biochemistry[Journal]


Mobile Loop in the Active Site of Metallocarboxypeptidases as an Underestimated Determinant of Substrate Specificity.

Biochemistry (Mosc) 2018 Dec;83(12):1594-1602

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.

It is generally accepted that the primary specificity of metallocarboxypeptidases is mainly determined by the structure of the so-called primary specificity pocket. However, the G215S/A251G/T257A/D260G/T262D mutant of carboxypeptidase T from Thermoactinomyces vulgaris (CPT) with the primary specificity pocket fully reproducing the one in pancreatic carboxypeptidase B (CPB) retained the broad, mainly hydrophobic substrate specificity of the wild-type enzyme. In order to elucidate factors affecting substrate specificity of metallocarboxypeptidases and the reasons for the discrepancy with the established views, we have solved the structure of the complex of the CPT G215S/A251G/T257A/D260G/T262D mutant with the transition state analogue N-sulfamoyl-L-phenylalanine at a resolution of 1. Read More

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http://dx.doi.org/10.1134/S0006297918120167DOI Listing
December 2018

Alternate and Additional Functions of Erythrocyte Hemoglobin.

Biochemistry (Mosc) 2018 Dec;83(12):1575-1593

Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Moscow, 119071, Russia.

The review discusses pleiotropic effects of erythrocytic hemoglobin (Hb) and their significance for human health. Hemoglobin is mostly known as an oxygen carrier, but its biochemical functions are not limited to this. The following aspects of Hb functioning are examined: (i) catalytic functions of the heme component (nitrite reductase, NO dioxygenase, monooxygenase, alkylhydroperoxidase) and of the apoprotein (esterase, lipoxygenase); (ii) participation in nitric oxide metabolism; (iii) formation of membrane-bound Hb and its role in the regulation of erythrocyte metabolism; (iv) physiological functions of Hb catabolic products (iron, CO, bilirubin, peptides). Read More

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http://dx.doi.org/10.1134/S0006297918120155DOI Listing
December 2018

Iatrogenic Damage of Eye Tissues: Current Problems and Possible Solutions.

Biochemistry (Mosc) 2018 Dec;83(12):1563-1574

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.

Visual system is at high risk of iatrogenic damage. Laser ocular surgery, the use of powerful illumination devices in diagnostics and surgical treatment of eye diseases, as well as long surgeries under general anesthesia provoke the development of chronic degenerative changes in eye tissues, primarily in the cornea and the retina. Despite the existence of approaches for prevention and treatment of these complications, the efficacy of these approaches is often limited. Read More

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http://dx.doi.org/10.1134/S0006297918120143DOI Listing
December 2018

Application of the CRISPR/Cas System for Generation of Pathogen-Resistant Plants.

Biochemistry (Mosc) 2018 Dec;83(12):1552-1562

Doka-Gene Technology Ltd., 141880 Rogachevo, Moscow Region, Russia.

The use of the CRISPR/Cas9 prokaryotic adaptive immune system has led to a breakthrough in targeted genome editing in eukaryotes. The CRISPR/Cas technology allows to generate organisms with desirable characteristics by introducing deletions/insertions into selected genome loci resulting in the knockout or modification of target genes. This review focuses on the current state of the CRISPR/Cas use for the generation of plants resistant to viruses, bacteria, and parasitic fungi. Read More

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http://dx.doi.org/10.1134/S0006297918120131DOI Listing
December 2018

Non-structural Functions of Hordeivirus Capsid Protein Identified in Plants Infected by a Chimeric Tobamovirus.

Biochemistry (Mosc) 2018 Dec;83(12):1543-1551

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.

Capsid proteins (CPs) of (+)RNA-containing plant viruses are multifunctional proteins involved in many stages of viral infection cycle, in addition to their main function of virus capsid formation. For example, the tobamoviral CP ensures virus systemic transport in plants and defines the virus-host interactions, thereby influencing the virus host range, virus infectivity, pathogenicity, and manifestation of infection symptoms. Hordeiviruses and tobamoviruses belong to the Virgaviridae family and have rod-shaped virions with a helical symmetry; their CPs are similar in structure. Read More

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http://dx.doi.org/10.1134/S000629791812012XDOI Listing
December 2018

Potential Markers of Autoimmune Diseases, Alleles rs115662534(T) and rs548231435(C), Disrupt the Binding of Transcription Factors STAT1 and EBF1 to the Regulatory Elements of Human CD40 Gene.

Biochemistry (Mosc) 2018 Dec;83(12):1534-1542

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.

CD40 receptor is expressed on B lymphocytes and other professional antigen-presenting cells. The binding of CD40 to its ligand CD154 on the surface of T helper cells plays an important role in the activation of B lymphocytes required for production of antibodies, in particular, against autoantigens. Association of several single nucleotide polymorphisms (SNPs) located in the non-coding areas of human CD40 locus with the elevated risk of autoimmune diseases has been demonstrated. Read More

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http://dx.doi.org/10.1134/S0006297918120118DOI Listing
December 2018

Can Aging be Programmed?

Authors:
J Mitteldorf

Biochemistry (Mosc) 2018 Dec;83(12):1524-1533

National Institute of Biological Sciences, Beijing, 102206, China.

Aging diminishes individual fitness, and aging could never evolve as an adaptive program according to the most prevalent model of evolutionary theory. On the other hand, some mechanisms of aging have been found to be conserved since the Cambrian explosion, and the physiology of aging sometimes looks like programmed self-destruction. Biostatisticians find evidence of an epigenetic aging clock, extending the clock that controls the growth and development into a realm of inexorably increasing mortality. Read More

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http://dx.doi.org/10.1134/S0006297918120106DOI Listing
December 2018

An Incipient Revolution in the Testing of Anti-aging Strategies.

Authors:
J Mitteldorf

Biochemistry (Mosc) 2018 Dec;83(12):1517-1523

School of Medicine, Washington University of St. Louis, MO 63130, USA.

Recent advances in the technology of "aging clocks" based on DNA methylation suggest that it may soon be possible to measure changes in the rate of human aging over periods as short as a year or two. If this potential is realized, the testing of putative anti-aging interventions will become radically cheaper and faster. This should prompt a re-appraisal of the entire spectrum of methods for evaluating anti-aging technologies in humans and in model systems. Read More

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http://dx.doi.org/10.1134/S000629791812009XDOI Listing
December 2018

Can Aging Develop as an Adaptation to Optimize Natural Selection? (Application of Computer Modeling for Searching Conditions When the "Fable of Hares" Can Explain the Evolution of Aging).

Biochemistry (Mosc) 2018 Dec;83(12):1504-1516

Lomonosov Moscow State University, Biological Faculty, Moscow, 119991, Russia.

There are two points of view on the evolution of aging. The classical theory of aging suggests that natural selection does not efficiently eliminate mutations or alleles that are harmful to organisms at later age. Another hypothesis is that the genetic program of aging has evolved as an adaptation that contributes to the optimization of the evolutionary process. Read More

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http://dx.doi.org/10.1134/S0006297918120088DOI Listing
December 2018

Ants as Object of Gerontological Research.

Biochemistry (Mosc) 2018 Dec;83(12):1489-1503

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.

Social insects with identical genotype that form castes with radically different lifespans are a promising model system for studying the mechanisms underlying longevity. The main direction of progressive evolution of social insects, in particular, ants, is the development of the social way of life inextricably linked with the increase in the colony size. Only in a large colony, it is possible to have a developed polyethism, create large food reserves, and actively regulate the nest microclimate. Read More

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http://dx.doi.org/10.1134/S0006297918120076DOI Listing
December 2018

Elimination of Senescent Cells: Prospects According to the Subtelomere-Telomere Theory.

Biochemistry (Mosc) 2018 Dec;83(12):1477-1488

Federico II University, Department of Translational Medical Sciences, Naples, 80138, Italy.

Cell senescence is an artificially reversible condition activated by various factors and characterized by replicative senescence and typical general alteration of cell functions, including extra-cellular secretion. The number of senescent cells increases with age and contributes strongly to the manifestations of aging. For these reasons, research is under way to obtain "senolytic" compounds, defined as drugs that eliminate senescent cells and therefore reduce aging-associated decay, as already shown in some experiments on animal models. Read More

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http://dx.doi.org/10.1134/S0006297918120064DOI Listing
December 2018

Role of Epithelial-Mesenchymal Transition in Tumor Progression.

Biochemistry (Mosc) 2018 Dec;83(12):1469-1476

Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478, Russia.

Epithelial-mesenchymal transition (EMT) is a fundamental process of morphogenesis whereby epithelial cells acquire the mesenchymal phenotype. Multiple data suggest a critical role of EMT in tumor progression. In carcinomas, EMT can be initiated and promoted by many oncogenic signaling pathways, hypoxia, and signals of tumor microenvironment resulting in epithelial cells losing their cell polarity and cell-cell adhesion and gaining the migratory and invasive properties. Read More

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http://dx.doi.org/10.1134/S0006297918120052DOI Listing
December 2018

Common and Specific Functions of Nonmuscle Myosin II Paralogs in Cells.

Biochemistry (Mosc) 2018 Dec;83(12):1459-1468

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Various forms of cell motility critically depend on pushing, pulling, and resistance forces generated by the actin cytoskeleton. Whereas pushing forces largely depend on actin polymerization, pulling forces responsible for cell contractility and resistance forces maintaining the cell shape require interaction of actin filaments with the multivalent molecular motor myosin II. In contrast to muscle-specific myosin II paralogs, nonmuscle myosin II (NMII) functions in virtually all mammalian cells, where it executes numerous mechanical tasks. Read More

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http://dx.doi.org/10.1134/S0006297918120040DOI Listing
December 2018

Alterations in WNT Signaling in Leukemias.

Biochemistry (Mosc) 2018 Dec;83(12):1448-1458

Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia.

The WNT/β-catenin signaling pathway plays an important role in the differentiation and proliferation of hematopoietic cells. In recent years, special attention has been paid to the role of impairments in the WNT signaling pathway in pathogenesis of malignant neoplasms of the hematopoietic system. Disorders in the WNT/β-catenin signaling in leukemias identified to date include hypersensitivity to the WNT ligands, epigenetic repression of WNT antagonists, overexpression of WNT ligands, impaired β-catenin degradation in the cytoplasm, and changes in the activity of the TCF/Lef transcription factors. Read More

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http://dx.doi.org/10.1134/S0006297918120039DOI Listing
December 2018

Cytomegalovirus Infection in Cardiovascular Diseases.

Biochemistry (Mosc) 2018 Dec;83(12):1437-1447

Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Atherosclerosis underlies the development of many cardiovascular diseases that continue to hold a leading place among the causes of death in developed countries. The role of activated immune cells in atherosclerosis progression has been convincingly demonstrated, but the mechanism of their action remains poorly investigated. Since atherosclerosis is associated with chronic inflammatory response, involvement of viral and bacterial infections in atherogenesis has been examined. Read More

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http://dx.doi.org/10.1134/S0006297918120027DOI Listing
December 2018

Juri Markovich Vasiliev - My Mentor and Friend.

Authors:
L B Margolis

Biochemistry (Mosc) 2018 Dec;83(12):1433-1436

Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119991, Russia.

This is an overview of the biography and scientific accomplishments of Dr. Juri Vasiliev, an outstanding Russian cell biologist. Ju. Read More

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http://dx.doi.org/10.1134/S0006297918120015DOI Listing
December 2018

Acetylation Enhances mRNA Stability and Translation.

Biochemistry 2019 Mar 15. Epub 2019 Mar 15.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences , Peking University , Beijing 100871 , China.

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http://dx.doi.org/10.1021/acs.biochem.9b00061DOI Listing

Quantifying the oligomeric state of hZIP4 on the surface of cells.

Biochemistry 2019 Mar 15. Epub 2019 Mar 15.

The human (h) zinc transporter ZIP4 is expressed on the plasma membrane and functions to increase cytosolic zinc levels. Mutations in hZIP4 cause the disease Acrodermatitis Enteropathica (AE). Dysfunction in the regulation of hZIP4 has also been indicated in solid tissue cancers, including pancreatic and prostate cancer. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00131DOI Listing

The Hsp90 Chaperone: H and F Dynamic NMR Spectroscopy Reveals A Perfect Enzyme.

Biochemistry 2019 Mar 14. Epub 2019 Mar 14.

Hsp90 is a crucial chaperone whose ATPase activity is fundamental for stabilizing and activating a diverse array of client proteins. Binding and hydrolysis of ATP by dimeric Hsp90 drives a conformational cycle characterized by fluctuations between a compact, N- and C-terminally dimerized catalytically competent closed state, and less compact open state which is largely C-terminally dimerized. We used F and H dynamic NMR spectroscopy to study the opening and closing kinetics of Hsp90, and to determine the k for ATP hydrolysis. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00144DOI Listing
March 2019
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Larotrectinib in NTRK-Rearranged Solid Tumors.

Biochemistry 2019 Mar 13. Epub 2019 Mar 13.

Section of Medical Oncology, Department of Medicine , Yale School of Medicine , New Haven , Connecticut 06520 , United States.

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http://dx.doi.org/10.1021/acs.biochem.9b00126DOI Listing

Coupling nucleotide binding and hydrolysis to iron-sulfur cluster acquisition and transfer revealed through genetic dissection of the Nbp35 ATPase site.

Biochemistry 2019 Mar 13. Epub 2019 Mar 13.

The cytosolic iron sulfur cluster assembly (CIA) scaffold, comprising Nbp35 and Cfd1 in yeast, assembles iron sulfur (FeS) clusters destined for cytosolic and nuclear enzymes. ATP hydrolysis by the CIA scaffold plays an essential but poorly understood role in cluster biogenesis. Here we find that mutation of conserved residues in the four motifs comprising the ATPase site of Nbp35 diminished the scaffold's ability to both assemble and transfer its FeS cluster in vivo. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b00737DOI Listing

Synthetic Epigenetics To Engineer Regulation.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

Departments of Biomedical Engineering, Chemistry, and Molecular Biology & Biochemistry , University of California , 3120 Natural Sciences II , Irvine , California 92697 , United States.

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http://dx.doi.org/10.1021/acs.biochem.9b00157DOI Listing

The thioredoxin system reduces protein persulfide intermediates formed during the synthesis of thio-cofactors in Bacillus subtilis.

Biochemistry 2019 Mar 11. Epub 2019 Mar 11.

The biosynthesis of Fe-S clusters and other thio-cofactors requires the participation of redox agents. A shared feature in these pathways is the formation of transient protein persulfides, which are susceptible to reduction by artificial reducing agents commonly used in reactions in vitro. These agents modulate the reactivity and catalytic efficiency of biosynthetic reactions and, in some cases, skew the enzymes' kinetic behavior, bypassing sulfur acceptors known to be critical for the functionality of these pathways in vivo. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00045DOI Listing

Structures of class Id ribonucleotide reductase catalytic subunits reveal a minimal architecture for deoxynucleotide biosynthesis.

Biochemistry 2019 Mar 11. Epub 2019 Mar 11.

Class I ribonucleotide reductases (RNRs) share a common mechanism of nucleotide reduction in a catalytic α subunit. All RNRs initiate catalysis with a thiyl radical, generated in class I enzymes by a metallocofactor in a separate β subunit. Class Id RNRs use a simple mechanism of cofactor activation involving oxidation of a Mn cluster by free superoxide to yield a metal-based MnMn oxidant. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01252DOI Listing

Menaquinone Biosynthesis: Biochemical and Structural Studies on chorismate dehydratase.

Biochemistry 2019 Mar 11. Epub 2019 Mar 11.

Menaquinone (MK, vitamin K) is a lipid soluble quinone that participates in the bacterial electron transport chain. In mammalian cells, vitamin K functions as an essential vitamin for the activation of several proteins involved in blood clotting and bone metabolism. MqnA is the first enzyme on the futalosine-dependent pathway to menaquinone and catalyzes the aromatization of chorismate by water loss. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00105DOI Listing

Specific and Selective Inhibitors of Proprotein Convertases Engineered by Transferring Serpin B8 Reactive-Site and Exosite Determinants of Reactivity to the Serpin α1PDX.

Biochemistry 2019 Mar 8. Epub 2019 Mar 8.

Department of Biochemistry and Structural Biology, Institute of Cellular Physiology , National Autonomous University of Mexico , Mexico City 04510 , Mexico.

The molecular determinants of substrate specificity and selectivity in the proprotein convertase (PC) family of proteases are poorly understood. Here we demonstrate that the natural serpin family inhibitor, serpin B8, is a specific and selective inhibitor of furin relative to the other PCs of the constitutive protein secretion pathway, PC4, PC5, PACE4, and PC7 (PC4-PC7, respectively), and identify reactive-site (P6-P5' residues) and exosite elements of the serpin that contribute to this specificity and selectivity through studies of chimeras of serpin B8 and α1PDX, an engineered serpin inhibitor of furin. Kinetic studies revealed that the specificity and selectivity of the serpin chimeras for inhibiting PCs were determined by P6-P5 and P3-P2 residue-dependent recognition of the P4Arg-X-X-P1Arg PC consensus sequence and exosite-dependent recognition of the reactive loop P2' residue of the chimeras by the PCs. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01295DOI Listing
March 2019
3.015 Impact Factor

Molecular Determinants of Temperature-Sensitive Phenotypes.

Biochemistry 2019 Mar 15. Epub 2019 Mar 15.

Molecular Biophysics Unit , Indian Institute of Science , Bangalore 560012 , India.

Temperature-sensitive (Ts) mutants are important tools for understanding the role of essential gene(s), but their molecular basis is not well understood. We use CcdB ( Controller of Cell Death protein B) as a model system to explore the effects of Ts mutations on protein stability, folding, and ligand binding. Previously isolated Ts CcdB mutants fall broadly into two categories, namely, buried site (<5% accessibility) and active site (involved in DNA gyrase binding). Read More

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http://dx.doi.org/10.1021/acs.biochem.8b00964DOI Listing

A Transition-State Perspective on Y-Family DNA Polymerase η Fidelity in Comparison with X-Family DNA Polymerases λ and β.

Biochemistry 2019 Mar 14. Epub 2019 Mar 14.

Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts, and Sciences , University of Southern California , University Park Campus , Los Angeles , California 90089 , United States.

Deoxynucleotide misincorporation efficiencies can span a wide 10-fold range, from ∼10 to ∼10, depending principally on polymerase (pol) identity and DNA sequence context. We have addressed DNA pol fidelity mechanisms from a transition-state (TS) perspective using our "tool-kit" of dATP- and dGTP-β,γ substrate analogues in which the pyrophosphate leaving group (p K = 8.9) has been replaced by a series of bisphosphonates covering a broad acidity range spanning p K values from 7. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00087DOI Listing
March 2019
1 Read
3.015 Impact Factor

Synthesis of Formate from CO Gas Catalyzed by an O-tolerant NAD-Dependent Formate Dehydrogenase and Glucose Dehydrogenase.

Biochemistry 2019 Mar 6. Epub 2019 Mar 6.

Direct biocatalytic conversion of CO to formic acid is an attractive means of reversibly storing energy in chemical bonds. Formate dehydrogenases (FDHs) are a heterogeneous group of enzymes that catalyze the oxidation of formic acid to carbon dioxide , generating two protons and two electrons. Several FDHs have recently been reported to catalyze the reverse reaction, i. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01301DOI Listing

Spectral Tuning by a Single Nucleotide Controls the Fluorescence Properties of a Fluorogenic Aptamer.

Biochemistry 2019 Mar 11. Epub 2019 Mar 11.

Department of Pharmacology, Weill Medical College , Cornell University , New York , New York 10065 , United States.

Fluorogenic aptamers are genetically encoded RNA aptamers that bind and induce the fluorescence of otherwise nonfluorescent small molecule dyes. These RNA-fluorophore complexes can be highly fluorescent and useful for RNA visualization and genetically encoded biosensors. Notably, different RNA aptamers can bind the same fluorophore, resulting in complexes that exhibit spectrally distinct fluorescence properties. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00048DOI Listing
March 2019
5 Reads

X-ray Structures of Two Bacteroides thetaiotaomicron C11 Proteases in Complex with Peptide-Based Inhibitors.

Biochemistry 2019 Mar 14. Epub 2019 Mar 14.

Departments of Molecular Medicine and Integrative Structural and Computational Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.

Commensal bacteria secrete proteins and metabolites to influence host intestinal homeostasis, and proteases represent a significant constituent of the components at the host:microbiome interface. Here, we determined the structures of the two secreted C11 cysteine proteases encoded by the established gut commensal Bacteroides thetaiotaomicron. We employed mutational analysis to demonstrate the two proteases, termed "thetapain" and "iotapain", undergo in trans autoactivation after lysine and/or arginine residues, as observed for other C11 proteases. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00098DOI Listing
March 2019
3 Reads

The Crg1 N-Terminus Is Essential for Methyltransferase Activity and Cantharidin Resistance in Saccharomyces cerevisiae.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

Laboratory of Chromatin Biology, Department of Biological Sciences , Indian Institute of Science Education and Research Bhopal , Bhopal 462066 , Madhya Pradesh , India.

Crg1 is an S-adenosylmethionine (SAM)-dependent methyltransferase required for cantharidin resistance in yeast. Crg1 has a well-characterized methyltransferase domain that inactivates cantharidin by methylation. However, the remaining part of the Crg1 protein is yet to be functionally characterized. Read More

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http://pubs.acs.org/doi/10.1021/acs.biochem.8b01277
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http://dx.doi.org/10.1021/acs.biochem.8b01277DOI Listing
March 2019
1 Read

Structural Basis of Lysosomal Phospholipase A Inhibition by Zn.

Biochemistry 2019 Mar 13. Epub 2019 Mar 13.

Departments of Biological Sciences and of Medicinal Chemistry & Molecular Pharmacology , Purdue University , West Lafayette , Indiana 47907 , United States.

Lysosomal phospholipase A (LPLA/PLA2G15) is a key enzyme involved in lipid homeostasis and is characterized by both phospholipase A2 and transacylase activity and by an acidic pH optimum. Divalent cations such as Ca and Mg have previously been shown to have little effect on the activity of LPLA, but the discovery of a novel crystal form of LPLA with Zn bound in the active site suggested a role for this divalent cation in regulating enzyme activity. In this complex, the cation directly coordinates the serine and histidine of the α/β-hydrolase triad and stabilizes a closed conformation. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01124DOI Listing

Identification of the Functional Roles of Six Key Proteins in the Biosynthesis of Enterobacteriaceae Colanic Acid.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

When subjected to harsh conditions such as low pH, pathogenic Escherichia coli can secrete colanic acid to establish a protective barrier between the organism and the acidic environment. The colanic acid consists of a six-sugar repeating unit polymer comprised of glucose, fucose, galactose, and glucuronic acid. The region of the E. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00040DOI Listing

Multiplex Genome Engineering for Optimizing Bioproduction in Saccharomyces cerevisiae.

Biochemistry 2019 Mar 8. Epub 2019 Mar 8.

Manchester Institute of Biotechnology (MIB), School of Chemistry , The University of Manchester , 131 Princess Street , Manchester M1 7DN , United Kingdom.

The field of synthetic biology is already beginning to realize its potential, with a wealth of examples showcasing the successful genetic engineering of microorganisms for the production of valuable compounds. The chassis Saccharomyces cerevisiae has been engineered to function as a microfactory for producing many of these economically and medically relevant compounds. However, strain construction and optimization to produce industrially relevant titers necessitate a wealth of underpinning biological knowledge alongside large investments of capital and time. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01086DOI Listing

Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome.

Biochemistry 2019 Mar 13. Epub 2019 Mar 13.

Institute of Pharmacy and Biochemistry , Johannes Gutenberg-Universität Mainz , 55128 Mainz , Germany.

The deficiency of the molybdenum cofactor (Moco) is an autosomal recessive disease, which leads to the loss of activity of all molybdoenzymes in humans with sulfite oxidase being the essential protein. Moco deficiency generally results in death in early childhood. Moco is a sulfur-containing cofactor synthesized in the cytosol with the sulfur being provided by a sulfur relay system composed of the l-cysteine desulfurase NFS1, MOCS3, and MOCS2A. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01160DOI Listing

Using Peptide Arrays To Discover the Sequence-Specific Acetylation of the Histidine-Tyrosine Dyad.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

Department of Chemistry , Northwestern University , Evanston , Illinois 60208 , United States.

Reactions that can selectively modify amino acid sequences within peptides and proteins are important for preparing protein reagents, immobilizing proteins, and making antibody-drug conjugates. The development of new reactions often begins with known chemistries and optimizes yields using a small set of peptide reactants. This article describes the use of peptide arrays and self-assembled monolayers for matrix-assisted laser desorption/ionization mass spectrometry (SAMDI-MS) to discover and characterize unanticipated sequence-selective reactions of peptides. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00022DOI Listing

Na/K Pump Mutations Associated with Primary Hyperaldosteronism Cause Loss of Function.

Biochemistry 2019 Mar 14. Epub 2019 Mar 14.

Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research , Texas Tech University Health Sciences Center , Lubbock , Texas 79430 , United States.

Primary hyperaldosteronism (Conn's syndrome), a common cause of secondary hypertension, is frequently produced by unilateral aldosterone-producing adenomas that carry mutations in ion-transporting genes, including ATP1A1, encoding the Na/K pump's α1 subunit. Whether Na/K pump mutant-mediated inward currents are required to depolarize the cell and increase aldosterone production remains unclear, as such currents were observed in four out of five mutants described so far. Here, we use electrophysiology and uptake of the K congener Rb, to characterize the effects of eight additional Na/K pump mutations in transmembrane segments TM1 (delM102-L103, delL103-L104, and delM102-I106), TM4 (delI322-I325 and I327S), and TM9 (delF956-E961, delF959-E961, and delE960-L964), expressed in Xenopus oocytes. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00051DOI Listing
March 2019
2 Reads

Structural and Functional Characterization of Sulfonium Carbon-Oxygen Hydrogen Bonding in the Deoxyamino Sugar Methyltransferase TylM1.

Biochemistry 2019 Feb 27. Epub 2019 Feb 27.

The N-methyltransferase TylM1 from Streptomyces fradiae catalyzes the final step in the biosynthesis of the deoxyamino sugar mycaminose, a substituent of the antibiotic tylosin. The high-resolution crystal structure of TylM1 bound to the methyl donor S-adenosylmethionine (AdoMet) illustrates a network of carbon-oxygen (CH•••O) hydrogen bonds between the substrate's sulfonium cation and residues within the active site. These interactions include hydrogen bonds between the methyl and methylene groups of the AdoMet sulfonium cation and the hydroxyl groups of Tyr14 and Ser120 in the enzyme. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01141DOI Listing
February 2019

Mechanism of 6-Hydroxynicotinate 3-Monooxygenase, a Flavin-Dependent Decarboxylative Hydroxylase Involved in Bacterial Nicotinic Acid Degradation.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

Department of Chemistry , The College of Wooster , Wooster , Ohio 44691 , United States.

6-Hydroxynicotinate 3-monooxygenase (NicC) is a Group A FAD-dependent monooxygenase that catalyzes the decarboxylative hydroxylation of 6-hydroxynicotinic acid (6-HNA) to 2,5-dihydroxypyridine (2,5-DHP) with concomitant oxidation of NADH in nicotinic acid degradation by aerobic bacteria. Two mechanisms for the decarboxylative hydroxylation half-reaction have been proposed [Hicks, K., et al. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b00969DOI Listing

Transition-State Interactions in a Promiscuous Enzyme: Sulfate and Phosphate Monoester Hydrolysis by Pseudomonas aeruginosa Arylsulfatase.

Biochemistry 2019 Mar 27;58(10):1363-1378. Epub 2019 Feb 27.

Department of Biochemistry , University of Cambridge , Cambridge , United Kingdom.

Pseudomonas aeruginosa arylsulfatase (PAS) hydrolyzes sulfate and, promiscuously, phosphate monoesters. Enzyme-catalyzed sulfate transfer is crucial to a wide variety of biological processes, but detailed studies of the mechanistic contributions to its catalysis are lacking. We present linear free energy relationships (LFERs) and kinetic isotope effects (KIEs) of PAS and analyses of active site mutants that suggest a key role for leaving group (LG) stabilization. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b00996DOI Listing

Identification of Factors Complicating Bioluminescence Imaging.

Biochemistry 2019 Mar 11. Epub 2019 Mar 11.

Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, Department of Chemistry, and UVA Cancer Center , University of Virginia , 1340 Jefferson Park Avenue , Charlottesville , Virginia 22908 , United States.

In vivo bioluminescence imaging (BLI) has become a standard, non-invasive imaging modality for following gene expression or the fate of proteins and cells in living animals. Currently, bioluminescent reporters used in laboratories are mostly derivatives of two major luciferase families: ATP-dependent insect luciferases and ATP-independent marine luciferases. Inconsistent results of experiments using different bioluminescent reporters, such as Akaluc and Antareas2, have been reported. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01303DOI Listing

Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice.

Biochemistry 2019 Mar 12. Epub 2019 Mar 12.

School of Chemistry & Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332-0400 , United States.

Mutations in myocilin, predominantly within its olfactomedin (OLF) domain, are causative for the heritable form of open angle glaucoma in humans. Surprisingly, mice expressing Tyr423His mutant myocilin, corresponding to a severe glaucoma-causing mutation (Tyr437His) in human subjects, exhibit a weak, if any, glaucoma phenotype. To address possible protein-level discrepancies between mouse and human OLFs, which might lead to this outcome, biophysical properties of mouse OLF were characterized for comparison with those of human OLF. Read More

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http://pubs.acs.org/doi/10.1021/acs.biochem.8b01309
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http://dx.doi.org/10.1021/acs.biochem.8b01309DOI Listing
March 2019
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Complex between a Multicrossover DNA Nanostructure, PX-DNA, and T7 Endonuclease I.

Biochemistry 2019 Mar 1;58(10):1332-1342. Epub 2019 Mar 1.

Department of Chemistry and Chemical Biology , Rensselaer Polytechnic Institute , Troy , New York 12180 , United States.

Paranemic crossover DNA (PX-DNA) is a four-stranded multicrossover structure that has been implicated in recombination-independent recognition of homology. Although existing evidence has suggested that PX is the DNA motif in homologous pairing (HP), this conclusion remains ambiguous. Further investigation is needed but will require development of new tools. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00057DOI Listing

A Disease-Causing Intronic Point Mutation C19G Alters Tau Exon 10 Splicing via RNA Secondary Structure Rearrangement.

Biochemistry 2019 Mar 7. Epub 2019 Mar 7.

Division of Chemistry & Biological Chemistry, School of Physical and Mathematical Sciences , Nanyang Technological University , 637371 Singapore.

Alternative splicing of MAPT cassette exon 10 produces tau isoforms with four microtubule-binding repeat domains (4R) upon exon inclusion or three repeats (3R) upon exon skipping. In human neurons, deviations from the ∼1:1 physiological 4R:3R ratio lead to frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Certain FTDP-17-associated mutations affect a regulatory hairpin that sequesters the exon 10 5' splice site (5'ss, located at the exon 10-intron 10 junction). Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00001DOI Listing

A Shared Mechanism for the Folding of Voltage-Gated K Channels.

Biochemistry 2019 Mar 7. Epub 2019 Mar 7.

Program in Chemical Biology, Department of Physiology and Pharmacology , Oregon Health & Science University , 3181 Southwest Sam Jackson Park Road , Portland , Oregon 97239 , United States.

In this study, we probe the folding of KAP, a voltage-gated K (K) channel. The KAP channel, though of archaebacterial origin, is structurally and functionally similar to eukaryotic K channels. An advantage of the KAP channel is that it can be folded in vitro from an extensively unfolded state and the folding can be controlled by temperature. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00068DOI Listing

The Thermodynamics of Ligand Binding to the Aminoglycoside O-Nucleotidyltransferase(4') and Variants Yields Clues about Thermophilic Properties.

Biochemistry 2019 Mar 6. Epub 2019 Mar 6.

Department of Biochemistry and Cellular and Molecular Biology , The University of Tennessee , Knoxville , Tennessee 37996 , United States.

The aminoglycoside nucleotidyltransferase(4') is an enzyme with high substrate promiscuity and catalyzes the transfer of the AMP group from ATP to the 4'-OH site of many structurally diverse aminoglycosides, which results in the elimination of their effectiveness as antibiotics. Two thermostable variants carrying single-site mutations are used to determine the molecular properties associated with thermophilicity. The thermodynamics of enzyme-ligand interactions showed that one variant (T130K) has properties identical to those of the mesophilic wild type (WT) while the other (D80Y) behaved differently. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01201DOI Listing

Investigating Substrate Analogues for Mycobacterial MenJ: Truncated and Partially Saturated Menaquinones.

Biochemistry 2019 Mar 6. Epub 2019 Mar 6.

Menaquinones (MKs) are essential for electron transport in prokaryotes, and importantly, partially saturated MKs represent a novel virulence factor. However, little is known regarding how the degree of saturation in the isoprenyl side chain influences conformation or quinone redox potential. MenJ is an enzyme that selectively reduces the second isoprene unit on MK-9 and is contextually essential for the survival of Mycobacterium tuberculosis in J774A. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00007DOI Listing

A New Microbial Pathway for Organophosphonate Degradation Catalyzed by Two Previously Misannotated Non-Heme-Iron Oxygenases.

Biochemistry 2019 Mar 7. Epub 2019 Mar 7.

The assignment of biochemical functions to hypothetical proteins is challenged by functional diversification within many protein structural superfamilies. This diversification, which is particularly common for metalloenzymes, renders functional annotations that are founded solely on sequence and domain similarities unreliable and often erroneous. Definitive biochemical characterization to delineate functional subgroups within these superfamilies will aid in improving bioinformatic approaches for functional annotation. Read More

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http://dx.doi.org/10.1021/acs.biochem.9b00044DOI Listing

Antioxidative Pseudoenzymatic Mechanism of NAD(P)H Coexisting with Oxyhemoglobin for Suppressed Methemoglobin Formation.

Biochemistry 2019 Mar 28;58(10):1400-1410. Epub 2019 Feb 28.

Department of Chemistry , Nara Medical University , 840 Shijo-cho , Kashihara , Nara 634-8521 , Japan.

Oxyhemoglobin (HbO) coexisting with equimolar NADH retards autoxidation and oxidant-induced metHb formation based on the pseudocatalase (CAT) and pseudosuperoxide dismutase (SOD) activities. In this work, we compared the effects of NADH with those of NADPH and estimated the binding site of NAD(P)H to HbO to elucidate the antioxidative mechanisms. The results clarified that pseudo-CAT and pseudo-SOD activities of HbO coexisting with NADPH were similar to activities obtained with NADH. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01314DOI Listing