{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:23:03Z","timestamp":1777591383530,"version":"3.51.4"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>(1) Background: ochratoxins are mycotoxins produced by filamentous fungi with important implications in the food manufacturing industry due to their toxicity. Decontamination by specific ochratoxin-degrading enzymes has become an interesting alternative for the treatment of contaminated food commodities. (2) Methods: using a structure-based approach based on homology modeling, blind molecular docking of substrates and characterization of low-frequency protein motions, we performed a proteome mining in filamentous fungi to characterize new enzymes with potential ochratoxinase activity. (3) Results: the proteome mining results demonstrated the ubiquitous presence of fungal binuclear zinc-dependent amido-hydrolases with a high degree of structural homology to the already characterized ochratoxinase from Aspergillus niger. Ochratoxinase-like enzymes from ochratoxin-producing fungi showed more favorable substrate-binding pockets to accommodate ochratoxins A and B. (4) Conclusions: filamentous fungi are an interesting and rich source of hydrolases potentially capable of degrading ochratoxins, and could be used for the detoxification of diverse food commodities.<\/jats:p>","DOI":"10.3390\/biom11071040","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:52:58Z","timestamp":1626432778000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Systematic Structure-Based Search for Ochratoxin-Degrading Enzymes in Proteomes from Filamentous Fungi"],"prefix":"10.3390","volume":"11","author":[{"given":"Ana L\u00facia","family":"Leit\u00e3o","sequence":"first","affiliation":[{"name":"MEtRICs, Department of Sciences and Technology of Biomass, NOVA School of Science and Technology, FCT NOVA, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-8557","authenticated-orcid":false,"given":"Francisco J.","family":"Enguita","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/2051112a0","article-title":"Ochratoxin A, a toxic metabolite produced by Aspergillus ochraceus Wilh","volume":"205","author":"Steyn","year":"1965","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10068-017-0288-7","article-title":"Determination of potentially mycotoxigenic fungi in coffee (Coffea arabica L.) from Nayarit","volume":"27","year":"2018","journal-title":"Food Sci. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"581309","DOI":"10.3389\/fmicb.2020.581309","article-title":"Comparative Genomic Analysis of Ochratoxin A Biosynthetic Cluster in Producing Fungi: New Evidence of a Cyclase Gene Involvement","volume":"11","author":"Ferrara","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0014-5793(77)81037-5","article-title":"Inhibition of phenylalanine tRNA synthetase from Bacillus subtilis by ochratoxin A","volume":"83","author":"Konrad","year":"1977","journal-title":"FEBS Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.toxlet.2012.03.800","article-title":"Ochratoxin A induces oxidative DNA damage and G1 phase arrest in human peripheral blood mononuclear cells in vitro","volume":"211","author":"Liu","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s00204-021-02993-6","article-title":"Ochratoxin A induces nephrotoxicity in vitro and in vivo via pyroptosis","volume":"95","author":"Li","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.toxlet.2019.05.021","article-title":"Ochratoxin A exerts neurotoxicity in human astrocytes through mitochondria-dependent apoptosis and intracellular calcium overload","volume":"313","author":"Park","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.reprotox.2015.05.017","article-title":"Ochratoxin A at low concentrations inhibits in vitro growth of canine umbilical cord matrix mesenchymal stem cells through oxidative chromatin and DNA damage","volume":"57","author":"Rutigliano","year":"2015","journal-title":"Reprod. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1590\/S0100-879X2006001200006","article-title":"DNA damage by ochratoxin A in rat kidney assessed by the alkaline comet assay","volume":"39","author":"Zeljezic","year":"2006","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1080\/19440049.2010.497166","article-title":"Mycotoxin food and feed regulation and the specific case of ochratoxin A: A review of the worldwide status","volume":"27","author":"Duarte","year":"2010","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3390\/toxins2051078","article-title":"Biodegradation of Ochratoxin A for Food and Feed Decontamination","volume":"2","author":"Abrunhosa","year":"2010","journal-title":"Toxins"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.4315\/0362-028X.JFP-16-160","article-title":"Heat Stability of Ochratoxin A in an Aqueous Buffered Model System","volume":"79","author":"Dahal","year":"2016","journal-title":"J. Food Prot."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.foodchem.2015.01.098","article-title":"Thermal stability and kinetics of degradation of deoxynivalenol, deoxynivalenol conjugates and ochratoxin A during baking of wheat bakery products","volume":"178","author":"Vidal","year":"2015","journal-title":"Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.3390\/toxins2071718","article-title":"Chemical, physical and biological approaches to prevent ochratoxin induced toxicoses in humans and animals","volume":"2","author":"Varga","year":"2010","journal-title":"Toxins"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.4315\/0362-028X.JFP-18-557","article-title":"Effects of Gamma Irradiation on Ochratoxin A Stability and Cytotoxicity in Methanolic Solutions and Potential Application in Tunisian Millet Samples","volume":"82","author":"Maatouk","year":"2019","journal-title":"J. Food Prot."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1021\/jf9030585","article-title":"Removal of ochratoxin A from contaminated red wines by repassage over grape pomaces","volume":"58","author":"Solfrizzo","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Raj, J., Vasiljevic, M., Tassis, P., Farkas, H., Bosnjak-Neumuller, J., and Manner, K. (2021). Effects of a modified clinoptilolite zeolite on growth performance, health status and detoxification of aflatoxin B1 and ochratoxin A in male broiler chickens. Br. Poult. Sci.","DOI":"10.1080\/00071668.2021.1891522"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/19440049.2010.551300","article-title":"The effect of chemical treatment on reduction of aflatoxins and ochratoxin A in black and white pepper during washing","volume":"28","author":"Jalili","year":"2011","journal-title":"Food Addit. Contam Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.4315\/0362-028X-71.7.1422","article-title":"A simple chemical method reduces ochratoxin A in contaminated cocoa shells","volume":"71","author":"Amezqueta","year":"2008","journal-title":"J. Food Prot."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"114","DOI":"10.5713\/ajas.2011.11104","article-title":"Isolation, screening and identification of Swine gut microbiota with ochratoxin a biodegradation ability","volume":"25","author":"Upadhaya","year":"2012","journal-title":"Asian Australas. J. Anim. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1128\/aem.47.5.1070-1073.1984","article-title":"Metabolism of aflatoxin, ochratoxin, zearalenone, and three trichothecenes by intact rumen fluid, rumen protozoa, and rumen bacteria","volume":"47","author":"Kiessling","year":"1984","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.2527\/1999.7751217x","article-title":"Metabolism and excretion of ochratoxin A fed to sheep","volume":"77","author":"Hohler","year":"1999","journal-title":"J. Anim. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.4014\/jmb.1606.06016","article-title":"Biodegradation of Ochratoxin A by Aspergillus tubingensis Isolated from Meju","volume":"26","author":"Cho","year":"2016","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.3390\/toxins7124864","article-title":"Biodegradation of Ochratoxin A by Bacterial Strains Isolated from Vineyard Soils","volume":"7","author":"Tristezza","year":"2015","journal-title":"Toxins"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijfoodmicro.2014.07.019","article-title":"Biodegradation of ochratoxin A by Pediococcus parvulus isolated from Douro wines","volume":"188","author":"Abrunhosa","year":"2014","journal-title":"Int. J. Food Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lyagin, I., and Efremenko, E. (2019). Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action. Molecules, 24.","DOI":"10.3390\/molecules24132362"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0006-2952(69)90224-X","article-title":"The hydrolysis of ochratoxin a by some proteolytic enzymes","volume":"18","author":"Pitout","year":"1969","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/08905430600904369","article-title":"Degradation of Ochratoxin A by Proteases and by a Crude Enzyme of Aspergillus niger","volume":"20","author":"Abrunhosa","year":"2006","journal-title":"Food Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s10529-007-9479-2","article-title":"Isolation and purification of an enzyme hydrolyzing ochratoxin A from Aspergillus niger","volume":"29","author":"Abrunhosa","year":"2007","journal-title":"Biotechnol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1042\/BJ20140382","article-title":"Structural and functional characterization of ochratoxinase, a novel mycotoxin-degrading enzyme","volume":"462","author":"Dobritzsch","year":"2014","journal-title":"Biochem. J."},{"key":"ref_31","first-page":"301","article-title":"The NCBI. Publicly available tools and resources on the Web","volume":"132","author":"Jenuth","year":"2000","journal-title":"Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/j.bpj.2011.10.024","article-title":"Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization","volume":"101","author":"Xu","year":"2011","journal-title":"Biophys. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","article-title":"CB-Dock: A web server for cavity detection-guided protein-ligand blind docking","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00894-019-4232-z","article-title":"Enhanced GROMACS: Toward a better numerical simulation framework","volume":"25","author":"Rakhshani","year":"2019","journal-title":"J. Mol. Model."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1002\/jcc.24829","article-title":"CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules","volume":"38","author":"Kim","year":"2017","journal-title":"J. Comput. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/bioinformatics\/btx349","article-title":"MD-TASK: A software suite for analyzing molecular dynamics trajectories","volume":"33","author":"Brown","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fmolb.2017.00087","article-title":"Recent Developments and Applications of the MMPBSA Method","volume":"4","author":"Wang","year":"2017","journal-title":"Front. Mol. Biosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1002\/jcc.24467","article-title":"Calculating protein-ligand binding affinities with MMPBSA: Method and error analysis","volume":"37","author":"Wang","year":"2016","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa\u2014A GROMACS Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.csbj.2020.03.011","article-title":"Caretta\u2014A multiple protein structure alignment and feature extraction suite","volume":"18","author":"Akdel","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Letunic, I., and Bork, P. (2021). Interactive Tree Of Life (iTOL) v5: An online tool for phylogenetic tree display and annotation. Nucleic Acids Res.","DOI":"10.1093\/nar\/gkab301"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: An improved methodology to estimate and visualize evolutionary conservation in macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.str.2016.11.012","article-title":"PyMOL and Inkscape Bridge the Data and the Data Visualization","volume":"24","author":"Yuan","year":"2016","journal-title":"Structure"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1107\/S0907444904023716","article-title":"Developments in the CCP4 molecular-graphics project","volume":"60","author":"Potterton","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/(SICI)1097-0134(19981115)33:3<417::AID-PROT10>3.0.CO;2-8","article-title":"Analysis of domain motions by approximate normal mode calculations","volume":"33","author":"Hinsen","year":"1998","journal-title":"Proteins"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tiwari, S.P., Fuglebakk, E., Hollup, S.M., Skjaerven, L., Cragnolini, T., Grindhaug, S.H., Tekle, K.M., and Reuter, N. (2014). WEBnm@ v2.0: Web server and services for comparing protein flexibility. BMC Bioinform., 15.","DOI":"10.1186\/s12859-014-0427-6"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1093\/bioinformatics\/btaa009","article-title":"The Protein Imager: A full-featured online molecular viewer interface with server-side HQ-rendering capabilities","volume":"36","author":"Tomasello","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Liu, A., and Huo, L. (2014). Amidohydrolase Superfamily. ELS, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470015902.a0020546.pub2"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s10822-017-0040-7","article-title":"Binding mode prediction and MD\/MMPBSA-based free energy ranking for agonists of REV-ERB\u03b1\/NCoR","volume":"31","author":"Westermaier","year":"2017","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D374","DOI":"10.1093\/nar\/gki023","article-title":"Fungal BLAST and Model Organism BLASTP Best Hits: New comparison resources at the Saccharomyces Genome Database (SGD)","volume":"33","author":"Balakrishnan","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"016008","DOI":"10.1088\/1478-3975\/9\/1\/016008","article-title":"Rapid simulation of protein motion: Merging flexibility, rigidity and normal mode analyses","volume":"9","author":"Freedman","year":"2012","journal-title":"Phys. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1021\/jf000413j","article-title":"Screening of commercial hydrolases for the degradation of ochratoxin A","volume":"48","author":"Stander","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1574-6968.2005.00073.x","article-title":"Biodegradation of ochratoxin A by Aspergillus section Nigri species isolated from French grapes: A potential means of ochratoxin A decontamination in grape juices and musts","volume":"255","author":"Bejaoui","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dellafiora, L., Gonaus, C., Streit, B., Galaverna, G., Moll, W.D., Vogtentanz, G., Schatzmayr, G., Dall\u2019Asta, C., and Prasad, S. (2020). An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme. Toxins, 12.","DOI":"10.3390\/toxins12040258"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6791","DOI":"10.1021\/bi100897u","article-title":"Functional identification and structure determination of two novel prolidases from cog1228 in the amidohydrolase superfamily","volume":"49","author":"Xiang","year":"2010","journal-title":"Biochemistry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1039\/C7SC04905F","article-title":"Cation-pi interactions in protein-ligand binding: Theory and data-mining reveal different roles for lysine and arginine","volume":"9","author":"Kumar","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s12013-012-9463-x","article-title":"Cation-pi interactions in beta-lactamases: The role in structural stability","volume":"66","author":"Lavanya","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/chem.201503761","article-title":"Cation-pi Interactions Contribute to Substrate Recognition in gamma-Butyrobetaine Hydroxylase Catalysis","volume":"22","author":"Kamps","year":"2016","journal-title":"Chemistry"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sommer, T., Bjerregaard-Andersen, K., Uribe, L., Etzerodt, M., Diezemann, G., Gauss, J., Cascella, M., and Morth, J.P. (2018). A fundamental catalytic difference between zinc and manganese dependent enzymes revealed in a bacterial isatin hydrolase. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31259-y"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ijfoodmicro.2017.12.028","article-title":"Description of an orthologous cluster of ochratoxin A biosynthetic genes in Aspergillus and Penicillium species. A comparative analysis","volume":"268","author":"Vazquez","year":"2018","journal-title":"Int. J. Food Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13762","DOI":"10.1074\/jbc.M513266200","article-title":"The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity","volume":"281","author":"Lohkamp","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/febs.13579","article-title":"Crystal structure of D-stereospecific amidohydrolase from Streptomyces sp. 82F2-insight into the structural factors for substrate specificity","volume":"283","author":"Arima","year":"2016","journal-title":"FEBS J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.febslet.2014.01.060","article-title":"The crystal structure of the amidohydrolase VinJ shows a unique hydrophobic tunnel for its interaction with polyketide substrates","volume":"588","author":"Shinohara","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/cbic.201200628","article-title":"Flexibility and reactivity in promiscuous enzymes","volume":"14","author":"Hollfelder","year":"2013","journal-title":"ChemBioChem"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.abb.2004.08.006","article-title":"Zinc hydrolases: The mechanisms of zinc-dependent deacetylases","volume":"433","author":"Hernick","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Mitic, N., Smith, S.J., Neves, A., Guddat, L.W., Gahan, L.R., and Schenk, G. (2006). Catalytic mechanism of binuclear metallohydrolases. Chem. Rev., 106.","DOI":"10.1021\/cr050318f"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1040\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:55Z","timestamp":1760164255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":71,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11071040"],"URL":"https:\/\/doi.org\/10.3390\/biom11071040","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]}}}