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Exploring Strategies toward Synthetic Precision Control within Core-Shell Nanowires.

Acc Chem Res 2021 May 14. Epub 2021 May 14.

Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, United States.

ConspectusAchieving precision and reproducibility in terms of physical structure and chemical composition within arbitrary nanoscale systems remains a "holy grail" challenge for nanochemistry. Because nanomaterials possess fundamentally distinctive size-dependent electronic, optical, and magnetic properties with wide-ranging applicability, the ability to produce homogeneous and monodisperse nanostructures with precise size and shape control, while maintaining a high degree of sample quality, purity, and crystallinity, remains a key synthetic objective. Moreover, it is anticipated that the methodologies developed to address this challenge ought to be reasonably simple, scalable, mild, nontoxic, high-yield, and cost-effective, while minimizing reagent use, reaction steps, byproduct generation, and energy consumption. Read More

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An overview of ProTide technology and its implications to drug discovery.

Expert Opin Drug Discov 2021 May 14. Epub 2021 May 14.

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

Introduction: The ProTide technology is a phosphate (or phosphonate) prodrug method devised to deliver nucleoside monophosphate (or monophosphonate) intracellularly bypassing the key challenges of antiviral and anticancer nucleoside analogues. Three new antiviral drugs, exploiting this technology, have been approved by the FDA while others are in clinical studies as anticancer agents.

Areas Covered: The authors describe the origin and development of this technology and its incredible success in transforming the drug discovery of antiviral and anticancer nucleoside analogues. Read More

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Optical sensing of anions by macrocyclic and interlocked hosts.

Org Biomol Chem 2021 May 13. Epub 2021 May 13.

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.

The ubiquity of anions in biological and environmental systems has motivated the development of many novel anion receptors and sensors over the past two decades. Optical anion sensors, which undergo a spectral change in response to anion binding, are particularly desirable due to the technical simplicity and fast response time of such systems. A myriad of macrocyclic host molecules have been shown to be effective anion receptors and present a promising platform for elaboration into optical anion sensors by incorporation of an appropriate fluorogenic or chromogenic group. Read More

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Mechanism-Guided Development of Transition-Metal-Catalyzed C-N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source.

Acc Chem Res 2021 May 12. Epub 2021 May 12.

Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Korea.

ConspectusCatalytic reactions that construct carbon-nitrogen bonds are one of central themes in both synthetic and medicinal chemistry since the obtainable nitrogen-containing motifs are commonly encountered in natural products and have also seen a growing prominence as key structural features in marketed drugs and preclinical candidates. Pd-catalyzed cross-couplings, such as Buchwald-Hartwig amination, are at the forefront of such synthetic methods in practical settings. However, they require prefunctionalized substrates such as (hetero)aryl halides that must be prepared independently, often by multiple operations. Read More

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Discovering unknown human and mouse transcription factor binding sites and their characteristics from ChIP-seq data.

Proc Natl Acad Sci U S A 2021 May;118(20)

Biodiversity Research Center, Academia Sinica, 115 Taipei, Taiwan;

Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin immunoprecipitation followed by sequencing) data. Applying it to the latest ENCODE ChIP-seq data for human and mouse, we found that using the irreproducible discovery rate as a quality-control criterion resulted in many experiments being unnecessarily discarded. Read More

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Genome-wide identification of 5-methylcytosine sites in bacterial genomes by high-throughput sequencing of MspJI restriction fragments.

PLoS One 2021 11;16(5):e0247541. Epub 2021 May 11.

Research Department, New England Biolabs, Ipswich, Massachusetts, United States of America.

Single-molecule Real-Time (SMRT) sequencing can easily identify sites of N6-methyladenine and N4-methylcytosine within DNA sequences, but similar identification of 5-methylcytosine sites is not as straightforward. In prokaryotic DNA, methylation typically occurs within specific sequence contexts, or motifs, that are a property of the methyltransferases that "write" these epigenetic marks. We present here a straightforward, cost-effective alternative to both SMRT and bisulfite sequencing for the determination of prokaryotic 5-methylcytosine methylation motifs. Read More

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Comprehensive discovery of novel structured noncoding RNAs in 26 bacterial genomes.

RNA Biol 2021 May 10:1-16. Epub 2021 May 10.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

Comparative sequence analysis methods are highly effective for uncovering novel classes of structured noncoding RNAs (ncRNAs) from bacterial genomic DNA sequence datasets. Previously, we developed a computational pipeline to more comprehensively identify structured ncRNA representatives from individual bacterial genomes. This search process exploits the fact that genomic regions serving as templates for the transcription of structured RNAs tend to be present in longer than average noncoding 'intergenic regions' (IGRs) that are enriched in G and C nucleotides compared to the remainder of the genome. Read More

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Antimicrobial and enzyme-responsive multi-peptide surfaces for bone-anchored devices.

Mater Sci Eng C Mater Biol Appl 2021 Jun 16;125:112108. Epub 2021 Apr 16.

MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Moos Tower, 515 Delaware St. SE, Minneapolis, MN 55455, USA. Electronic address:

Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e. Read More

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π-Extended Nonfullerene Acceptors for Efficient Organic Solar Cells with a High Open-Circuit Voltage of 0.94 V and a Low Energy Loss of 0.49 eV.

ACS Appl Mater Interfaces 2021 May 6. Epub 2021 May 6.

Chinese Academy of Sciences (CAS) Key Laboratory of Nano System and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

A combination of high open-circuit voltage () and short-circuit current density () typically creates effective organic solar cells (OSCs). Y5, a member of the Y-series acceptors, can achieve high of 0.94 V with PM6 but low of 12. Read More

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Detection of a mosaic CDKL5 deletion and inversion by optical genome mapping ends an exhaustive diagnostic odyssey.

Mol Genet Genomic Med 2021 May 6:e1665. Epub 2021 May 6.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Background: Currently available structural variant (SV) detection methods do not span the complete spectrum of disease-causing SVs. Optical genome mapping (OGM), an emerging technology with the potential to resolve diagnostic dilemmas, was performed to investigate clinically-relevant SVs in a 4-year-old male with an epileptic encephalopathy of undiagnosed molecular origin.

Methods: OGM was utilized to image long, megabase-size DNA molecules, fluorescently labeled at specific sequence motifs throughout the genome with high sensitivity for detection of SVs greater than 500 bp in size. Read More

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Advances in Drug Discovery against Neglected Tropical Diseases: Human African and American Trypanosomiasis.

Curr Med Chem 2021 May 3. Epub 2021 May 3.

Medicinal Chemistry Research Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India.

Human African and American trypanosomiasis are the vector-borne parasitic diseases that have killed millions of people early, and many people are still suffering from these neglected diseases. The causative agents of these infections are parasitic protozoans of the genus Trypanosoma. Current treatment regimens against these endemic diseases have several limitations in terms of safety, efficacy, route of administration, and some of them have lost efficacy due to the emergence of resistance in their respective parasites. Read More

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Semi-permeable resonant aluminum gratings for structural coloration in transmission.

Opt Lett 2021 May;46(9):2200-2203

The novel type of diffraction gratings consists of a semi-permeable corrugated aluminum film with periods supporting first-order diffraction in the visible wavelength range. These gratings exhibit coloring of the transmitted zeroth order due to excitation of surface plasmons. The hue depends on the angle of incidence and may be adjusted by varying the grating period. Read More

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Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer.

Antib Ther 2021 Jan 9;4(1):16-33. Epub 2021 Feb 9.

Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Read More

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January 2021

Risk Assessment of Bovine Major Histocompatibility Complex Class II Alleles for Perinatal Transmission of Bovine Leukemia Virus.

Pathogens 2021 Apr 22;10(5). Epub 2021 Apr 22.

Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Perinatal transmission plays a critical role in the spread of bovine leukemia virus (BLV) infection in cattle herds. In the Holstein breed, we previously identified BLV resistant and susceptible bovine leukocyte antigen ()- alleles, including - and with a low BLV proviral load (PVL), and and with a high PVL. Here, we evaluated the perinatal BLV transmission risk in dams with different alleles. Read More

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Beneficial Effects of Cyclic Ether 2-Butoxytetrahydrofuran from Sea Cucumber against Aβ Aggregate Toxicity in Transgenic and Potential Chemical Interaction.

Molecules 2021 Apr 11;26(8). Epub 2021 Apr 11.

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

The pathological finding of amyloid-β (Aβ) aggregates is thought to be a leading cause of untreated Alzheimer's disease (AD). In this study, we isolated 2-butoxytetrahydrofuran (2-BTHF), a small cyclic ether, from and demonstrated its therapeutic potential against AD through the attenuation of Aβ aggregation in a transgenic model. Our results revealed that amongst the five isolated compounds, 2-BTHF was shown to be the most effective in suppressing worm paralysis caused by Aβ toxicity and in expressing strong neuroprotection in CL4176 and CL2355 strains, respectively. Read More

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Built to Last: Functional and Structural Mechanisms in the Moth Olfactory Network Mitigate Effects of Neural Injury.

Brain Sci 2021 Apr 5;11(4). Epub 2021 Apr 5.

Department of Applied Mathematics, University of Washington, Seattle, WA 98195-3925, USA.

Most organisms suffer neuronal damage throughout their lives, which can impair performance of core behaviors. Their neural circuits need to maintain function despite injury, which in particular requires preserving key system outputs. In this work, we explore whether and how certain structural and functional neuronal network motifs act as injury mitigation mechanisms. Read More

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In Vitro and In Silico Screening and Characterization of Antimicrobial Napin Bioactive Protein in and .

Molecules 2021 Apr 5;26(7). Epub 2021 Apr 5.

Department of Food Science and Biotechnology, College of Agriculture and Life Science, Kangwon National University, Chuncheon 24341, Korea.

The study aimed to investigate the antibacterial activity of Mustard () and Moringa () leaf extracts and coagulant protein for their potential application in water treatment. Bacterial cell aggregation and growth kinetics studies were employed for thirteen bacterial strains with different concentrations of leaf extracts and coagulant protein. leaf extract (MOS) and coagulant protein showed cell aggregation against ten bacterial strains, whereas leaf extract alone showed growth inhibition of five bacterial strains for up to 6 h and five bacterial strains for up to 3 h. Read More

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Imidazolinium -Heterocyclic Carbene Ligands for Enhanced Stability on Gold Surfaces.

Langmuir 2021 Apr 29. Epub 2021 Apr 29.

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, South Bend 46556, Indiana, United States.

-heterocyclic carbenes (NHCs) have emerged as versatile and robust ligands for noble metal surface modifications due to their ability to form compact, self-assembled monolayers. Despite a growing body of research, previous NHC surface modification schemes have employed just two structural motifs: the benzimidazolium NHC and the imidazolium NHC. However, different NHC moieties, including saturated NHCs, are often more effective in homogenous catalysis chemistry than these aforementioned motifs and may impart numerous advantages to NHC surfaces, such as increased stability and access to chiral groups. Read More

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Deciphering the key heterocyclic scaffolds in targeting microtubules, kinases and carbonic anhydrases for cancer drug development.

Pharmacol Ther 2021 Apr 22;225:107860. Epub 2021 Apr 22.

Medicinal Chemistry Research Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:

Heterocyclic scaffolds are widely utilized for drug design by taking into account the molecular structure of therapeutic targets that are related to a broad spectrum of ailments, including tumors. Such compounds display various covalent and non-covalent interactions with the specific residues of the target proteins while causing their inhibition. There is a substantial number of heterocyclic compounds approved for cancer treatment, and these compounds function by interacting with different therapeutic targets involved in tumorogenesis. Read More

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Host PDZ-containing proteins targeted by SARS-CoV-2.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Institut Pasteur, Unité Récepteurs-Canaux, UMR CNRS 3571, Paris, France.

Small linear motifs targeting protein interacting domains called PSD-95/Dlg/ZO-1 (PDZ) have been identified at the C terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins E, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E, 3A, and N showing significant interactions with dissociation constants values ranging from 3 to 82 μm. Six of them (TJP1, PTPN13, HTRA1, PARD3, MLLT4, LNX2) are also recognized by SARS-CoV while three (NHERF1, MAST2, RADIL) are specific to SARS-CoV-2 E protein. Read More

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Molecular engineering of carbon nitride towards photocatalytic H evolution and dye degradation.

J Colloid Interface Sci 2021 Sep 31;597:39-47. Epub 2021 Mar 31.

Department of Chemistry, Sri Siddhartha Institute of Technology, Tumkur 572105, Karnataka, India. Electronic address:

The development of superior heterogeneous catalyst for hydrogen (H) evolution is a significant feature and challenging for determining the energy and environmental crises. However, the dumping of numerous lethal colorants (dye) as of textile manufacturing has fascinated widespread devotion-aimed water pollution anticipation and treatment. In this regard, a photocatalytic H evolution by visible light using low-dimensional semiconducting materials having pollutant degradable capacity for Rhodamine B dyes (RhB) has been anticipated as a route towards environmental aspect. Read More

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September 2021

Biocatalysts Based on Peptide and Peptide Conjugate Nanostructures.

Authors:
Ian W Hamley

Biomacromolecules 2021 May 12;22(5):1835-1855. Epub 2021 Apr 12.

Department of Chemistry, University of Reading, RG6 6AD Reading, United Kingdom.

Peptides and their conjugates (to lipids, bulky N-terminals, or other groups) can self-assemble into nanostructures such as fibrils, nanotubes, coiled coil bundles, and micelles, and these can be used as platforms to present functional residues in order to catalyze a diversity of reactions. Peptide structures can be used to template catalytic sites inspired by those present in natural enzymes as well as simpler constructs using individual catalytic amino acids, especially proline and histidine. The literature on the use of peptide (and peptide conjugate) α-helical and β-sheet structures as well as turn or disordered peptides in the biocatalysis of a range of organic reactions including hydrolysis and a variety of coupling reactions (e. Read More

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Determination of amino acids that favour the α region using Ramachandran propensity plots. Implications for α-sheet as the possible amyloid intermediate.

J Struct Biol 2021 Apr 8;213(2):107738. Epub 2021 Apr 8.

College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address:

In amyloid diseases an insoluble amyloid fibril forms via a soluble oligomeric intermediate. It is this intermediate that mediates toxicity and it has been suggested, somewhat controversially, that it has the α-sheet structure. Nests and α-strands are similar peptide motifs in that alternate residues lie in the α and γ regions of the Ramachandran plot for nests, or α and α regions for α-strands. Read More

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LAPTM4α is targeted from the Golgi to late endosomes/lysosomes in a manner dependent on the E3 ubiquitin ligase Nedd4-1 and ESCRT proteins.

Biochem Biophys Res Commun 2021 Jun 6;556:9-15. Epub 2021 Apr 6.

Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address:

Lysosome-associated protein transmembrane 4α (LAPTM4α) is a four transmembrane-spanning protein primarily localized in endosomes and lysosomes and has several putative lysosomal targeting signals at its C-terminal cytoplasmic domain, including tyrosine-based motifs (YxxΦ) and PY motifs (L/PxxY). LAPTM4α has been previously shown to be ubiquitinated by the E3 ubiquitin ligase Nedd4-1 through binding to its PY motifs and sorted to lysosomes, however, the molecular mechanisms underlying the localization of LAPTM4α to endosomes/lysosomes have not yet been fully elucidated. In the present study, we show that LAPTM4α binds Nedd4-1 in a manner dependent on PY motifs, while the PY motifs and Nedd4-1 are not necessarily required for LAPTM4α ubiquitination. Read More

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Sequence and structure-based method to predict diacylglycerol lipases in protein sequence.

Int J Biol Macromol 2021 Apr 6;182:455-463. Epub 2021 Apr 6.

School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China. Electronic address:

Lipase enzymes play a central role in biotechnology and the food industry. Diacylglyceride lipases (DAG) have received considerable attention due to their physiological significance and potential industrial usage. However, compared to the wide application of triacylglycerol (TAG) lipases, DAG lipases have a limited application due to their low thermostability and specific activity. Read More

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Substituted Dihydropyridine Synthesis by Dearomatization of Pyridines.

Angew Chem Int Ed Engl 2021 Apr 8. Epub 2021 Apr 8.

Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149, Münster, Germany.

Dearomatization is an effective method to transform readily available N-heterocycles into partially saturated motifs. Manipulation of dihydro-derivatives holds great potential and provides access to a variety of semi-saturated N-heterocyclic building blocks. However, current strategies are limited in scope and the use of sensitive reagents restricts the applicability in synthetic laboratories. Read More

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Tau strains shape disease.

Acta Neuropathol 2021 Apr 8. Epub 2021 Apr 8.

Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Tauopathies consist of over 25 different neurodegenerative diseases that include argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD). Tauopathies are defined by brain accumulation of microtubule-associated protein tau in fibrillar aggregates, whose prevalence strongly correlates with dementia. Dominant mutations in tau cause neurodegenerative diseases, and most increase its aggregation propensity. Read More

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Mechanistic Diversity of Low-Valent Chromium Catalysis: Cross-Coupling and Hydrofunctionalization.

Acc Chem Res 2021 Apr 8;54(8):2014-2026. Epub 2021 Apr 8.

Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

ConspectusTransition-metal catalysis has traditionally been dominated by precious metals because of their high reactivity toward chemical transformations. As a cost-effective alternative, catalysis by earth-abundant group 6 metal chromium is underdeveloped, and its reactivity remains largely unexplored, although the industrially important Phillips catalyst, which is composed of Cr as the active metal, is currently used to supply almost 40% of the total world demand for high-density polyethylene. Cr has traditionally served in organoreagents with high-valent states (≥2+), which are typified by reactions involving Nozaki-Hiyama-Kishi (NHK) and Takai-Utimoto one-electron transfer processes. Read More

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The Importance of Therapeutically Targeting the Binary Toxin from .

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Novel therapeutics are needed to treat pathologies associated with the binary toxin (CDT), particularly when infection (CDI) occurs in the elderly or in hospitalized patients having illnesses, in addition to CDI, such as cancer. While therapies are available to block toxicities associated with the large clostridial toxins (TcdA and TcdB) in this nosocomial disease, nothing is available yet to treat toxicities arising from strains of CDI having the binary toxin. Like other binary toxins, the active CDTa catalytic subunit of CDT is delivered into host cells together with an oligomeric assembly of CDTb subunits via host cell receptor-mediated endocytosis. Read More

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Identification of metal binding motifs in protein frameworks to develop novel remediation strategies for Hg and Cr(VI).

Biometals 2021 Jun 2;34(3):621-638. Epub 2021 Apr 2.

Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamilnadu, 632014, India.

Amino acid sequences in metal-binding proteins with chelating properties offer exciting applications in biotechnology and medical research. To enhance their application in bioremediation studies, we explicitly aimed to identify specific metal-binding chelating motifs in protein structures for two significant pollutants, such as mercury (Hg) and chromium Cr(V1). For this purpose, we have performed an extensive coordination chemistry approach by retrieving Hg and Cr(V1) binding protein structures from the protein database and validated using the B-factor, a term defining uncertainty of the atoms and with occupancy to obtain the best binding motifs. Read More

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