3,193 results match your criteria catalytic triad


The structural features of an ancient ribonuclease from Salmo salar reveal an intriguing case of auto-inhibition.

Int J Biol Macromol 2021 Apr 10. Epub 2021 Apr 10.

Department of Biology, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Naples, Italy.

The superfamily of vertebrate ribonucleases, a large group of evolutionarily related proteins, continues to provide interesting structural and functional information. In particular, the crystal structure of SS-RNase-2 from Salmo salar (SS2), here presented, has revealed a novel auto-inhibition mechanism that enriches the number of inhibition strategies observed in some members of the family. Within an essentially unmodified RNase folding, the SS2 active site cleft is in part obstructed by the collapse of an extra pentapeptide inserted in the C-terminal region. Read More

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Structural basis for substrate specificity of the peroxisomal acyl-CoA hydrolase MpaH' involved in mycophenolic acid biosynthesis.

FEBS J 2021 Apr 12. Epub 2021 Apr 12.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong, 266237, China.

Mycophenolic acid (MPA) is a fungal natural product and first-line immunosuppressive drug for organ transplantations and autoimmune diseases. In the compartmentalized biosynthesis of MPA, the acyl-coenzyme A (CoA) hydrolase MpaH' located in peroxisomes catalyzes the highly specific hydrolysis of MPA-CoA to produce the final product MPA. The strict substrate specificity of MpaH' not only averts undesired hydrolysis of various cellular acyl-CoAs, but also prevents MPA-CoA from further peroxisomal β-oxidation catabolism. Read More

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-Aminobenzohydrazide Derivatives as Fatty Acid Amide Hydrolase Inhibitors: Design, Synthesis and Biological Evaluation.

Iran J Pharm Res 2020 ;19(4):103-112

Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The endocannabinoid system plays an important neuromodulatory role in the periphery and central nervous system, which can regulate several physiological processes. The inhibition of enzymatic activities responsible for hydrolysis anandamide and other endogenous fatty acid amides, enhances cannabinoid receptors activity indirectly that may prove to be useful drugs for the treatment of range of ailments including pain, anxiety, and other central nervous system disorders. In this study, we designed, synthesized, and evaluated novel fatty acid amide hydrolase (FAAH) inhibitors based on 4-aminobenzohydrazide derivatives. Read More

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January 2020

Biochemical and structural characterization of the BioZ enzyme engaged in bacterial biotin synthesis pathway.

Nat Commun 2021 04 6;12(1):2056. Epub 2021 Apr 6.

Department of Pathogen Biology & Microbiology and General Intensive Care Unit of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Biotin is an essential micro-nutrient across the three domains of life. The paradigm earlier step of biotin synthesis denotes "BioC-BioH" pathway in Escherichia coli. Here we report that BioZ bypasses the canonical route to begin biotin synthesis. Read More

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Structure-guided improvement in the enantioselectivity of an Aspergillus usamii epoxide hydrolase for the gram-scale kinetic resolution of ortho-trifluoromethyl styrene oxide.

Enzyme Microb Technol 2021 May 19;146:109778. Epub 2021 Mar 19.

Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, PR China. Electronic address:

Microtuning the substrate-binding pocket (SBP) of EHs has emerged as an effective approach to manipulate their enantio- or regio-selectivities and activities towards target substrates. Here, the enantioselectivity (enantiomeric ratio, E) of AuEH2 towards a racemic (rac-) ortho-trifluoromethyl styrene oxide (o-TFMSO) was improved via microtuning its SBP. Based on the analysis on the crystal structure of AuEH2, its specific residues I192, Y216, R322 and L344 lining the SBP in close to the catalytic triad were identified for site-saturation mutagenesis. Read More

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Cyanide Hydratase Modification Using Computational Design and Docking Analysis for Improved Binding Affinity in Cyanide Detoxification.

Molecules 2021 Mar 23;26(6). Epub 2021 Mar 23.

Department of Chemical Engineering, University of Johannesburg, Doornfontein, Johannesburg 2094, South Africa.

Cyanide is a hazardous and detrimental chemical that causes the inactivation of the respiration system through the inactivation of cytochrome c oxidase. Because of the limitation in the number of cyanide-degrading enzymes, there is a great demand to design and introduce new enzymes with better functionality. This study developed an integrated method of protein-homology-modelling and ligand-docking protein-design approaches that reconstructs a better active site from cyanide hydratase (CHT) structure. Read More

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Crystal structure of a GDP-6-OMe-4-keto-L-xylo-heptose reductase from Campylobacter jejuni.

Proteins 2021 Mar 31. Epub 2021 Mar 31.

Department of Chemistry, Chonnam National University, Gwangju, Republic of Korea.

Carbohydrates play a major role in infection strategies of various enteric pathogens. In Campylobacter jejuni, the most common cause of gastroenteritis, uniquely modified heptoses found in surface carbohydrates are synthesized by specific pathways. Owing to the importance of such pathways for the infectious potential of pathogens and/or their virulence, these biosynthesis pathways present potential targets for therapeutic intervention. Read More

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Properties of FDA-approved small molecule phosphatidylinositol 3-kinase inhibitors prescribed for the treatment of malignancies.

Authors:
Robert Roskoski

Pharmacol Res 2021 Mar 26;168:105579. Epub 2021 Mar 26.

Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742-8814, United States. Electronic address:

The discovery of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway was a major advance in understanding eukaryotic signal transduction. The high frequency of PI 3-kinase pathway mutations in many cancers stimulated the development of drugs targeting these oncogenic mutants. The PI 3-kinases are divided into three classes and Class I PI 3-kinases, which catalyze the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) to generate phosphatidylinositol-3,4,5-trisphosphate (PIP3), are the main subject of this review. Read More

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Screening of small molecule libraries using combined text mining, ligand- and target-driven based approaches for identification of novel granzyme H inhibitors.

J Mol Graph Model 2021 Feb 25;105:107876. Epub 2021 Feb 25.

Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey. Electronic address:

Granzymes are serine proteases synthesized by CTL and NK cells. Five granzyme genes (GzmA, -B, -H, -K, -M) are present in humans, which are located at three different chromosomal loci. Being serine proteases, the binding pocket constitutes a catalytic triad (i. Read More

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February 2021

Structural leitmotif and functional variations of the structural catalytic core in (chymo)trypsin-like serine/cysteine fold proteinases.

Int J Biol Macromol 2021 Mar 10;179:601-609. Epub 2021 Mar 10.

Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland.

Proteinases with the (chymo)trypsin-like serine/cysteine fold comprise a large superfamily performing their function through the Acid - Base - Nucleophile catalytic triad. In our previous work (Denesyuk AI, Johnson MS, Salo-Ahen OMH, Uversky VN, Denessiouk K. Int J Biol Macromol. Read More

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An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases.

J Biol Eng 2021 Mar 6;15(1). Epub 2021 Mar 6.

Department of Microbiology and Immunology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. Read More

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Molecular cloning and biochemical characterization of a trehalose synthase from Myxococcus sp. strain V11.

Protein Expr Purif 2021 Jul 4;183:105865. Epub 2021 Mar 4.

College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, 330045, PR China; Collaborative Innovation Center of Postharvest Key Technology and Quality Safety of Fruits and Vegetables in Jiangxi Province, Nanchang, 330045, PR China. Electronic address:

The tresI gene of Myxococcus sp. strain V11 was cloned, and found to encode a trehalose synthase comprising 551 amino acids. The deduced molecular weight of the encoded TreS I protein 64. Read More

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Atg15 in consists of two functionally distinct domains.

Mol Biol Cell 2021 Apr 24;32(8):645-663. Epub 2021 Feb 24.

Department of Integrated Biosciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan.

Autophagy is a cellular degradation system widely conserved among eukaryotes. During autophagy, cytoplasmic materials fated for degradation are compartmentalized in double membrane-bound organelles called autophagosomes. After fusing with the vacuole, their inner membrane-bound structures are released into the vacuolar lumen to become autophagic bodies and eventually degraded by vacuolar hydrolases. Read More

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Transition Path Sampling Study of the Feruloyl Esterase Mechanism.

J Phys Chem B 2021 03 22;125(8):2018-2030. Epub 2021 Feb 22.

Renewable Resources and Enabling Sciences Center, National Renewable Energy Laboratory, Golden, Colorado 80401, United States.

Serine hydrolases cleave peptide and ester bonds and are ubiquitous in nature, with applications in biotechnology, in materials, and as drug targets. The serine hydrolase two-step mechanism employs a serine-histidine-aspartate/glutamate catalytic triad, where the histidine residue acts as a base to activate poor nucleophiles (a serine residue or a water molecule) and as an acid to allow the dissociation of poor leaving groups. This mechanism has been the subject of debate regarding how histidine shuttles the proton from the nucleophile to the leaving group. Read More

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Comparative study of potyvirid NIa proteases and their cleavage sites.

Arch Virol 2021 Apr 18;166(4):1141-1149. Epub 2021 Feb 18.

Madurai Kamaraj University, Madurai, Tamil Nadu, India.

Nuclear inclusion a protease (NIaPro), a major protease of potyvirids, processes its cognate viral polyprotein at distinct cleavage sites. Although Potyviridae is the largest family of the realm Riboviria, the individual NIaPro enzymes and their cleavage sites are believed to be species-specific. In the present study, the NIaPro amino acid sequences of 165 potyvirids of 10 genera and their 1154 cleavage sites were compared to understand their genus/species-specificity and functional regulation. Read More

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Probing the Role of Catalytic Triad on the Cleavage between Intramolecular Chaperone and NK Mature Peptide.

J Agric Food Chem 2021 Feb 11;69(7):2348-2353. Epub 2021 Feb 11.

Beijing Key Laboratory of Plants Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China.

Many proteases require the assistance of an intramolecular chaperone (IMC) that is essential for protein folding. Subtilisin is produced as a precursor that requires its N-terminal propeptide to act as an IMC to chaperone the folding of its subtilisin domain. During the precursor folding, the cleavage of the peptide bond between the IMC and the subtilisin domain is the most important and rate-limiting step, which leads to the structural reorganization of the subtilisin domain and IMC's degradation. Read More

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February 2021

Crystal structure of fungal tannase from Aspergillus niger.

Acta Crystallogr D Struct Biol 2021 Feb 2;77(Pt 2):267-277. Epub 2021 Feb 2.

Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), 343 Royal Parade, Parkville, VIC 3052, Australia.

Tannases are serine esterases that were first discovered in fungi more than one and half centuries ago. They catalyze the hydrolysis of the gallolyl ester bonds in gallotannins to release gallic acid, which is an important intermediate in the chemical and pharmaceutical industries. Since their discovery, fungal tannases have found wide industrial applications, although there is scarce knowledge about these enzymes at the molecular level, including their catalytic and substrate-binding sites. Read More

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February 2021

Escherichia coli FabG 3-ketoacyl-ACP reductase proteins lacking the assigned catalytic triad residues are active enzymes.

J Biol Chem 2021 Feb 2:100365. Epub 2021 Feb 2.

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States of America; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States of America. Electronic address:

The FabG 3-ketoacyl-acyl carrier protein (ACP) reductase of Escherichia coli has long been thought to be a classical member of the short chain alcohol dehydrogenase/reductase (SDR) family. FabG catalyzes the essential 3-ketoacyl-ACP reduction step in the FAS II fatty acid synthesis pathway. Site-directed mutagenesis studies of several other SDR enzymes has identified three highly conserved amino acid residues, Ser, Tyr, and Lys, as the catalytic triad. Read More

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February 2021

Degradation of a Main Plastic Pollutant Polyethylene Terephthalate by Two Distinct Proteases (Neprilysin and Cutinase-like Enzyme).

J Chem Inf Model 2021 Feb 3;61(2):764-776. Epub 2021 Feb 3.

Department of Chemistry, University of Miami, Coral Gables, Florida 33146, United States.

In this DFT study, hydrolysis of polyethylene terephthalate (PET), a major cause of plastic pollution, by two distinct enzymes, neprilysin (, a mononuclear metalloprotease) and cutinase-like enzyme (, a serine protease), has been investigated. These enzymes utilize different mechanisms for the degradation of PET. uses either the metal-bound hydroxide attack (MH) mechanism or reverse protonation (RP) mechanism, while utilizes a general acid/base mechanism that includes acylation and deacylation processes. Read More

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February 2021

Light-mediated control of activity in a photosensitive foldamer that mimics an esterase.

Chem Commun (Camb) 2021 Mar;57(18):2269-2272

Department of Chemical Sciences, University of Padova, Padova 35131, Italy.

We report a catalytic foldamer in which a fumaramide chromophore links a Ser residue to a helical domain that contains within its sequence the residues His and Asp. Photoisomerization of the fumaramide chromophore (with E geometry) to the corresponding maleamide (with Z geometry) brings together a 'catalytic triad' of Ser, His, and Asp, triggering esterase activity that is absent in the fumaramide isomer. The fumaramide/maleamide linker thus acts as a light-sensitive switchable cofactor for activation of catalytic activity in short foldamers. Read More

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Molecular and Structural Characterizations of Lipases from by Functional Genomics.

Mar Drugs 2021 Jan 28;19(2). Epub 2021 Jan 28.

Laboratoire de Génie Enzymatique et de Microbiologie, Equipe de Biotechnologie des Algues, Ecole Nationale d'Ingénieurs de Sfax, Université de Sfax, Sfax 3038, Tunisia.

Microalgae have been poorly investigated for new-lipolytic enzymes of biotechnological interest. In silico study combining analysis of sequences homologies and bioinformatic tools allowed the identification and preliminary characterization of 14 putative lipases expressed by . These proteins have different molecular weights, subcellular localizations, low instability index range and at least 40% of sequence identity with other microalgal lipases. Read More

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January 2021

Structure-function studies of the C3/C5 epimerases and C4 reductases of the Campylobacter jejuni capsular heptose modification pathways.

J Biol Chem 2021 Jan 29:100352. Epub 2021 Jan 29.

Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, N6A 5C1, Canada. Electronic address:

Many bacteria produce polysaccharide-based capsules that protect them from environmental insults and play a role in virulence, host invasion, and other functions. Understanding how the polysaccharide components are synthesized could provide new means to combat bacterial infections. We have previously characterized two pairs of homologous enzymes involved in the biosynthesis of capsular sugar precursors GDP-6-deoxy-D-altro-heptose and GDP-6-OMe-L-gluco-heptose in Campylobacter jejuni. Read More

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January 2021

In vitro cholinesterase inhibitory action of L. Cannabaceae and in silico study of its selected phytocompounds.

In Silico Pharmacol 2021 21;9(1):13. Epub 2021 Jan 21.

Department of Biology, Faculty of Science, Razi University, 67149-67346 Kermanshah, Iran.

L. Cannabaceae, used for psychoactive rituals in Mesopotamia. Here, we investigated in vitro inhibitory activity of methyl alcohol extract derived from leaves and resin of cannabis against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Read More

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January 2021

Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24.

Extremophiles 2021 Mar 30;25(2):115-128. Epub 2021 Jan 30.

Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases and Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, College of Life Sciences, Anhui Normal University, Wuhu, 241000, Anhui, China.

A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Read More

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Characterization of the Nit6803 nitrilase homolog from the cyanotroph NCIMB 11764.

Biochem Biophys Rep 2021 Mar 16;25:100893. Epub 2021 Jan 16.

Division of Biochemistry and Molecular Biology, Department of Biological Sciences, University of North Texas, Denton, TX, 76203, USA.

We report the purification and characterization of a nitrilase (E.C. 3. Read More

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CE16 acetylesterases: in silico analysis, catalytic machinery prediction and comparison with related SGNH hydrolases.

3 Biotech 2021 Feb 19;11(2):84. Epub 2021 Jan 19.

Laboratory of Protein Evolution, Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava, Slovak Republic.

Bioinformatics analysis was focused on unique acetylesterases annotated in the CAZy database within the CE16 family and simultaneously belonging to the SGNH hydrolase superfamily. The CE16 acetylesterases were compared to structurally related SGNH hydrolases: (i) selected members of the CE2, CE3, CE6, CE12 and CE17 family of the CAZy database and (ii) structural representatives of the Lipase_GDSL and Lipase_GDSL_2 families according to the Pfam database. Sequence alignment based on four conserved sequence regions (CSRs) containing active-site residues was used to calculate sequence logos specific for each CE family and to construct a phylogenetic tree. Read More

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February 2021

Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, DD1 5EH, Scotland, United Kingdom

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Read More

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January 2021

Functional analysis of the catalytic triad of the hAT-family transposase TcBuster.

Plasmid 2021 Mar 18;114:102554. Epub 2021 Jan 18.

Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. Electronic address:

TcBuster is a hAT-family DNA transposon from the red flour beetle, Tribolium castaneum. The TcBuster transposase is of interest for genome engineering as it is highly active in insect and mammalian cells. To test the predicted catalytic triad of TcBuster, each residue of the catalytic triad of a haemagglutinin-tagged TcBuster transposase was individually mutated to a structurally conserved amino acid. Read More

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A phenylalanine dynamic switch controls the interfacial activation of Rhizopus chinensis lipase.

Int J Biol Macromol 2021 Mar 18;173:1-12. Epub 2021 Jan 18.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China. Electronic address:

The catalytic mechanism of most lipases involves a step called "interfacial activation" which significantly increases lipases activity beyond the critical micellar concentration (CMC) of substrate. In the present study, Rhizopus chinensis lipase (RCL) was used as a research model to explore the mechanism of lipase interfacial activation beyond the CMC. Molecular dynamic (MD) simulations indicated the open- and closed-lid transitions and revealed that Phe113 was the critical site for RCL activation by its dynamic flipping. Read More

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