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Comput Struct Biotechnol J 2021 26;19:970-975. Epub 2021 Jan 26.

Chair of Plant Physiology and Biotechnology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Lwowska St. 1, 87-100 Toruń, Poland.

Cyclic nucleotide monophosphates (cNMPs) are increasingly recognized as essential signaling molecules governing many physiological and developmental processes in prokaryotes and eukaryotes. Degradation of cNMPs is as important as their generation because it offers the capability for transient and dynamic cellular level regulation but unlike their generating enzymes, the degrading enzymes, cyclic nucleotide phosphodiesterases (PDEs) are somewhat elusive in higher plants. Based on sequence analysis and structural properties of canonical PDE catalytic centers, we have developed a consensus sequence search motif and used it to identify candidate PDEs. Read More

Sci Rep 2020 12 10;10(1):21678. Epub 2020 Dec 10.

Institute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori, Sennan-gun, Osaka, 590-0494, Japan.

Incoherent quasielastic neutron scattering (iQENS) is a fascinating technique for investigating the internal dynamics of protein. However, low flux of neutron beam, low signal to noise ratio of QENS spectrometers and unavailability of well-established analyzing method have been obstacles for studying internal dynamics under physiological condition (in solution). The recent progress of neutron source and spectrometer provide the fine iQENS profile with high statistics and as well the progress of computational technique enable us to quantitatively reveal the internal dynamic from the obtained iQENS profile. Read More

Protein Sci 2021 Feb 28;30(2):408-422. Epub 2020 Nov 28.

Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas, USA.

Transferrins function in iron sequestration and iron transport by binding iron tightly and reversibly. Vertebrate transferrins coordinate iron through interactions with two tyrosines, an aspartate, a histidine, and a carbonate anion, and conformational changes that occur upon iron binding and release have been described. Much less is known about the structure and functions of insect transferrin-1 (Tsf1), which is present in hemolymph and influences iron homeostasis mostly by unknown mechanisms. Read More

Chem Commun (Camb) 2020 Nov;56(92):14447-14450

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

We identified several CH-π donor-acceptor pairs involving amino acid side chains with less polarized C-H bonds at a solvent-exposed site between the strands of a β-hairpin peptide. Therein, we observe a distance-dependent induction of CH-π interaction within the aliphatic-aromatic amino acid pair. Our results also suggest an interplay of hydrophobicity and CH-π interaction in dictating the stability of β-hairpins, where a leucine-tryptophan pair contributes -1. Read More

J Biol Chem 2020 12 26;295(52):18226-18238. Epub 2020 Oct 26.

Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, NHLBI, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:

Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. Read More

Enzyme Microb Technol 2020 Nov 11;141:109632. Epub 2020 Jul 11.

Department of Food Science, Ontario Agricultural College, University of Guelph, Guelph, ON, N1G 2W1, Canada; Food, Nutrition, and Health Program, Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, V6T 1Z4 Canada. Electronic address:

Pepsin, the archetypal pepsin-like aspartic protease, is irreversibly denatured when exposed to neutral pH conditions whereas renin, a structural homologue of pepsin, is fully stable and optimally active in the same conditions despite sharing highly similar enzyme architecture. To gain insight into the structural determinants of differential aspartic protease pH stability, the present study used comparative bioinformatic and structural analyses. In pepsin, an abundance of polar and aspartic acid residues were identified, a common trait with other acid-stable enzymes. Read More

Mol Microbiol 2020 Oct 8. Epub 2020 Oct 8.

Department of Microbiology, University of Georgia, Athens, GA, USA.

The production of the pyrimidine moiety in thiamine synthesis, 2-methyl-4-amino-5-hydroxymethylpyrimidine phosphate (HMP-P), has been described to proceed through the Thi5-dependent pathway in Saccharomyces cerevisiae and other yeast. Previous work found that ScThi5 functioned poorly in a heterologous context. Here we report a bacterial ortholog to the yeast HMP-P synthase (Thi5) was necessary for HMP synthesis in Legionella pneumophila. Read More

FEBS J 2020 Aug 16. Epub 2020 Aug 16.

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Uni Paris-Sud, Uni Paris-Saclay, Gif-sur-Yvette Cedex, France.

Progeroid laminopathies are characterized by the premature appearance of certain signs of physiological aging in a subset of tissues. They are caused by mutations in genes coding for A-type lamins or lamin-binding proteins. Here, we review how different mutations causing progeroid laminopathies alter protein structure or protein-protein interactions and how these impact on mechanisms that protect cell viability and function. Read More

Biomolecules 2020 07 24;10(8). Epub 2020 Jul 24.

Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Because proteins are fundamental to most biological processes, many genetic diseases can be traced back to single nucleotide variants (SNVs) that cause changes in protein sequences. However, not all SNVs that result in amino acid substitutions cause disease as each residue is under different structural and functional constraints. Influential studies have shown that protein-protein interaction interfaces are enriched in disease-associated SNVs and depleted in SNVs that are common in the general population. Read More

Sci Rep 2020 07 13;10(1):11497. Epub 2020 Jul 13.

Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA.

One innate immune response in insects is the proteolytic activation of hemolymph prophenoloxidase (proPO), regulated by protease inhibitors called serpins. In the inhibition reaction of serpins, a protease cleaves a peptide bond in a solvent-exposed reactive center loop (RCL) of the serpin, and the serpin undergoes a conformational change, incorporating the amino-terminal segment of the RCL into serpin β-sheet A as a new strand. This results in an irreversible inhibitory complex of the serpin with the protease. Read More

J Biol Chem 2020 08 13;295(35):12474-12484. Epub 2020 Jul 13.

Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom

The D76N variant of human β-microglobulin (βm) is the causative agent of a hereditary amyloid disease. Interestingly, D76N-associated amyloidosis has a distinctive pathology compared with aggregation of WT-βm, which occurs in dialysis-related amyloidosis. A folding intermediate of WT-βm, known as the I-state, which contains a nonnative Pro-32, has been shown to be a key precursor of WT-βm aggregation However, how a single amino acid substitution enhances the rate of aggregation of D76N-βm and gives rise to a different amyloid disease remained unclear. Read More

Cell Chem Biol 2020 08 9;27(8):1084-1096.e4. Epub 2020 Jul 9.

Department of Chemistry, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address:

Solution-based structural techniques complement high-resolution structural data by providing insight into the oft-missed links between protein structure and dynamics. Here, we present Parallel Chemoselective Profiling, a solution-based structural method for characterizing protein structure and dynamics. Our method utilizes deep mutational scanning saturation mutagenesis data to install amino acid residues with specific chemistries at defined positions on the solvent-exposed surface of a protein. Read More

Biophys Chem 2020 09 29;264:106420. Epub 2020 Jun 29.

Institute of Special Environmental Medicine, Nantong University, No. 9, Seyuan Road, Nantong City, Jiangsu Province, People's Republic of China. Electronic address:

One notable feature of the SARS-CoV-2 genome, the spike (S) protein of SARS-CoV-2 has a polybasic furin cleavage site (FCS) at its S1-S2 boundary through the insertion of 12 nucleotides encoding four amino acid residues PRRA. Quite intriguingly, this polybasic FCS is absent in coronaviruses of the same clade as SARS-CoV-2. Thus, with currently available experimental structural data for S protein, this short article presents a set of comprehensive structural characterization of the insertion of FCS into S protein, and argues against a hypothesis of the origin of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS is spatially located at a random coil loop region, mostly distantly solvent-exposed (instead of deeply buried), with no structural proximity to the other part of the S protein; (2), the insertion of FCS itself does not alter, neither stabilize nor de-stabilize, the three-dimensional structure of S; (3), the net result here is the insertion of a furin cleavage site into S protein, whose S1 and S2 subunits will still be strongly electrostatically bonded together from a structural and biophysical point of view, even if the polybasic FCS is actually cleaved by furin protease before or after viral cell entry. Read More

J Bacteriol 2020 08 25;202(18). Epub 2020 Aug 25.

Department of Microbiology, University of Illinois, Urbana, Illinois, USA

Hydrogen peroxide (HO) is formed in natural environments by both biotic and abiotic processes. It easily enters the cytoplasms of microorganisms, where it can disrupt growth by inactivating iron-dependent enzymes. It also reacts with the intracellular iron pool, generating hydroxyl radicals that can lethally damage DNA. Read More

Front Genet 2020 12;11:489. Epub 2020 May 12.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.

Wheat powdery mildew caused by f. sp. () is a devastating disease that threatens wheat production and yield worldwide. Read More

Mol Pharm 2020 07 11;17(7):2555-2569. Epub 2020 Jun 11.

Biotherapeutics Discovery Department, Boehringer Ingelheim, Ridgefield, Connecticut 06877, United States.

The ability of antibodies to recognize their target antigens with high specificity is fundamental to their natural function. Nevertheless, therapeutic antibodies display variable and difficult-to-predict levels of nonspecific and self-interactions that can lead to various drug development challenges, including antibody aggregation, abnormally high viscosity, and rapid antibody clearance. Here we report a method for predicting the overall specificity of antibodies in terms of their relative risk for displaying high levels of nonspecific or self-interactions at physiological conditions. Read More

Biochemistry 2020 05 20;59(17):1672-1679. Epub 2020 Apr 20.

Here we show that a solvent-exposed -position (i.e., residue 14) within a well-characterized trimeric helix bundle can facilitate a stabilizing long-range synergistic interaction involving -position Glu10 (i. Read More

J Vis Exp 2020 03 11(157). Epub 2020 Mar 11.

Department of Pharmaceutical Sciences, University of Maryland Baltimore;

Fast photochemical oxidation of proteins (FPOP) is a hydroxyl radical protein footprinting method used to characterize protein structure and interactions. FPOP uses a 248 nm excimer laser to photolyze hydrogen peroxide producing hydroxyl radicals. These radicals oxidatively modify solvent exposed side chains of 19 of the 20 amino acids. Read More

Biochim Biophys Acta Biomembr 2020 06 4;1862(6):183260. Epub 2020 Mar 4.

Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, Alberta T2N 1N4, Canada. Electronic address:

Because of their potential as novel antibiotic agents, antimicrobial peptides (AMPs) have generated considerable interest. The mechanism of bacterial toxicity of AMPs often involves the disruption and/or permeabilization of the bacterial membrane; even those that act intracellularly first have to traverse the membrane. In this work we have explored the incorporation of the fluorinated aromatic amino acids fluoro-Phe and fluoro-Tyr into the Trp- and Arg-rich AMP tritrpticin, and investigated their role in the membrane binding properties and the antimicrobial activity of the peptide. Read More

Theranostics 2020 12;10(5):2172-2187. Epub 2020 Jan 12.

Lehrstuhl für Biologische Chemie, Technische Universität München, 85354 Freising, Germany.

Enhanced amino acid supply and dysregulated integrin signaling constitute two hallmarks of cancer and are pivotal for metastatic transformation of cells. In line with its function at the crossroads of both processes, overexpression of CD98hc is clinically observed in various cancer malignancies, thus rendering it a promising tumor target. : We describe the development of Anticalin proteins based on the lipocalin 2 (Lcn2) scaffold against the human CD98hc ectodomain (hCD98hcED) using directed evolution and protein design. Read More

Biochim Biophys Acta Biomembr 2020 05 23;1862(5):183204. Epub 2020 Jan 23.

School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia.

Little is known experimentally about the detailed orientation of membrane-bound maculatin 1.1 (Mac1), an antimicrobial peptide from the skin secretions of Australian tree frogs. In this work multiple N-labelled or H-labelled Mac1 with dodecylphosphocholine (DPC) micelles and isotropic DMPC/DHPC (q = 0. Read More

PLoS Negl Trop Dis 2020 01 10;14(1):e0007815. Epub 2020 Jan 10.

Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, México.

Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glycolysis and because those proteins elicit an immune response, presumably due to their surface localization. Here we report the crystal structures of TsTPI and SmTPI in complex with 2-phosphoglyceric acid (2-PGA). Read More

World J Microbiol Biotechnol 2019 Dec 19;36(1). Epub 2019 Dec 19.

Department of Biosciences, COMSATS University, Islamabad, Chak Shazad Campus, Islamabad, Pakistan.

Campylobacter jejuni is the one of the leading cause of bacterial food borne gastroenteritis. PglB, a glycosyltransferase, plays a crucial role of mediating glycosylation of numerous periplasmic proteins. It catalyzes N-glycosylation at the sequon D/E-X1-N-X2-S/T in its substrate proteins. Read More

PLoS Negl Trop Dis 2019 12 2;13(12):e0007919. Epub 2019 Dec 2.

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Current knowledge of the piRNA pathway is based mainly on studies on Drosophila melanogaster where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as dengue and chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma and cross-talk with proteins of recognized antiviral function cannot be excluded for some Piwi proteins. These observations underscore the importance of expanding our knowledge of the piRNA pathway beyond the model organism D. Read More

J Biol Inorg Chem 2019 12 10;24(8):1197-1215. Epub 2019 Oct 10.

Department of Chemistry, University of Copenhagen, Universitetsparken-5, 2100, Copenhagen, Denmark.

Aberrant aggregation of the Aβ protein is a hallmark of Alzheimer's disease (AD), but no complete characterization of the molecular level pathogenesis has been achieved. A promising hypothesis is that dysfunction of metal ion homeostasis, and consequently, the undesired interaction of metal ions with Aβ, may be central to the development of AD. Qualitatively, most data indicate that Cu(II) induces rapid self-assembly of both Aβ40 and Aβ42 during the initial phase of the aggregation, while at longer time scales fibrillation may occur, depending on the experimental conditions. Read More

Angew Chem Int Ed Engl 2019 12 21;58(49):17583-17588. Epub 2019 Oct 21.

Department or Pure and Applied Chemistry, University of Strathclyde, 298 Cathedral Street, Glasgow, G1 1XL, UK.

A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Read More

J Am Chem Soc 2019 10 15;141(42):16790-16801. Epub 2019 Oct 15.

Department of Chemistry and Howard Hughes Medical Institute , University of Illinois at Urbana-Champaign , Urbana , Illinois 61801 , United States.

Lanthipeptides represent a large class of cyclic natural products defined by the presence of lanthionine (Lan) and methyllanthionine (MeLan) cross-links. With the advances in DNA sequencing technologies and genome mining tools, new biosynthetic enzymes capable of installing unusual structural features are continuously being discovered. In this study, we investigated an -methyltransferase that is a member of the most prominent auxiliary enzyme family associated with class I lanthipeptide biosynthetic gene clusters. Read More

Curr Pharm Des 2019 ;25(31):3378-3389

Department of Biotechnology, Indian Institute of Technology, Roorkee-247667, Uttarakhand, India.

Background: Mostly BLIPs are identified in soil bacteria Streptomyces and originally isolated from Streptomyces clavuligerus and can be utilized as a model system for biophysical, structural, mutagenic and computational studies. BLIP possess homology with two proteins viz., BLIP-I (Streptomyces exofoliatus) and BLP (beta-lactamase inhibitory protein like protein from S. Read More

Chemistry 2019 Dec 6;25(67):15351-15360. Epub 2019 Nov 6.

IRIG, CBM, University of Grenoble Alpes, CEA, CNRS, 38000, Grenoble, France.

In Rhodospirillum rubrum, the maturation of carbon monoxide dehydrogenase (CODH) requires three nickel chaperones, namely RrCooC, RrCooT and RrCooJ. Recently, the biophysical characterisation of the RrCooT homodimer and the X-ray structure of its apo form revealed the existence of a solvent-exposed Ni -binding site at the dimer interface, involving the strictly conserved Cys2. Here, a multifaceted approach that used NMR and X-ray absorption spectroscopies, complemented with structural bio-modelling methodologies, was used to characterise the binding mode of Ni in RrCooT. Read More

Environ Sci Technol 2019 Sep 3;53(18):10845-10854. Epub 2019 Sep 3.

Department of Environmental Sciences , The Connecticut Agricultural Experiment Station , New Haven , Connecticut 06511 , United States.

A variety of peptidic and proteinaceous contaminants (e.g., proteins, toxins, pathogens) present in the environment may pose risk to human health and wildlife. Read More