{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:55:14Z","timestamp":1762102514816,"version":"3.41.2"},"reference-count":75,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":145,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P41GM103311"],"award-info":[{"award-number":["P41GM103311"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-0640476","DBI-0234768"],"award-info":[{"award-number":["DBI-0640476","DBI-0234768"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01GM07790","U54GM093342","DBI-1356193","R01GM60595"],"award-info":[{"award-number":["P01GM07790","U54GM093342","DBI-1356193","R01GM60595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Determining the molecular function of enzymes discovered by genome sequencing represents a primary foundation for understanding many aspects of biology. Historically, classification of enzyme reactions has used the enzyme nomenclature system developed to describe the overall reactions performed by biochemically characterized enzymes, irrespective of their associated sequences. In contrast, functional classification and assignment for the millions of protein sequences of unknown function now available is largely done in two computational steps, first by similarity-based assignment of newly obtained sequences to homologous groups, followed by transferring to them the known functions of similar biochemically characterized homologs. Due to the fundamental differences in their etiologies and practice, `how\u2019 these chemistry- and evolution-centric functional classification systems relate to each other has been difficult to explore on a large scale. To investigate this issue in a new way, we integrated two published ontologies that had previously described each of these classification systems independently. The resulting infrastructure was then used to compare the functional assignments obtained from each classification system for the well-studied and functionally diverse enolase superfamily. Mapping these function assignments to protein structure and reaction similarity networks shows a profound and complex disconnect between the homology- and chemistry-based classification systems. This conclusion mirrors previous observations suggesting that except for closely related sequences, facile annotation transfer from small numbers of characterized enzymes to the huge number uncharacterized homologs to which they are related is problematic. Our extension of these comparisons to large enzyme superfamilies in a computationally intelligent manner provides a foundation for new directions in protein function prediction for the huge proportion of sequences of unknown function represented in major databases. Interactive sequence, reaction, substrate and product similarity networks computed for this work for the enolase and two other superfamilies are freely available for download from the Structure Function Linkage Database Archive (http:\/\/sfld.rbvi.ucsf.edu).<\/jats:p>","DOI":"10.1093\/database\/baaa034","type":"journal-article","created":{"date-parts":[[2020,5,3]],"date-time":"2020-05-03T03:20:45Z","timestamp":1588476045000},"source":"Crossref","is-referenced-by-count":6,"title":["A strategy for large-scale comparison of evolutionary- and reaction-based classifications of enzyme function"],"prefix":"10.1093","volume":"2020","author":[{"given":"Gemma L","family":"Holliday","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"},{"name":"Present Address: Medicines Discovery Catapult, Mereside, Alderley Park, Alderley Edge SK10 4TG, UK"}]},{"given":"Shoshana D","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"}]},{"given":"David","family":"Mischel","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"}]},{"given":"Benjamin J","family":"Polacco","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"}]},{"given":"Patricia C","family":"Babbitt","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"},{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"},{"name":"Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, 1700 4th Street, CA 94143, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"2020052504194914000_ref1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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Rev. Biochem."},{"key":"2020052504194914000_ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.mie.2018.06.004","article-title":"Atlas of the radical SAM superfamily: divergent evolution of function using a \"plug and play\" domain","volume":"606","author":"Holliday","year":"2018","journal-title":"Methods Enzymol."},{"key":"2020052504194914000_ref31","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0022-2836(02)00649-6","article-title":"One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions","volume":"321","author":"Nagano","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2020052504194914000_ref32","doi-asserted-by":"crossref","first-page":"e1000605","DOI":"10.1371\/journal.pcbi.1000605","article-title":"Annotation error in public databases: misannotation of molecular function in enzyme superfamilies","volume":"5","author":"Schnoes","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2020052504194914000_ref33","doi-asserted-by":"crossref","first-page":"D351","DOI":"10.1093\/nar\/gky1100","article-title":"InterPro in 2019: improving coverage, classification and access to protein sequence annotations","volume":"47","author":"Mitchell","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020052504194914000_ref34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/database\/bax006","article-title":"Biocuration in the structure-function linkage database: the anatomy of a superfamily","volume":"2017","author":"Holliday","year":"2017","journal-title":"Database (Oxford)"},{"key":"2020052504194914000_ref35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cbpa.2011.03.008","article-title":"Toward mechanistic classification of enzyme functions","volume":"15","author":"Almonacid","year":"2011","journal-title":"Curr. Opin. Chem. Biol."},{"key":"2020052504194914000_ref36","doi-asserted-by":"crossref","first-page":"e1000142","DOI":"10.1371\/journal.pcbi.1000142","article-title":"Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies","volume":"4","author":"Chiang","year":"2008","journal-title":"PLoS Comput. Biol."},{"key":"2020052504194914000_ref37","doi-asserted-by":"crossref","first-page":"D427","DOI":"10.1093\/nar\/gky995","article-title":"The Pfam protein families database in 2019","volume":"47","author":"El-Gebali","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020052504194914000_ref38","doi-asserted-by":"crossref","first-page":"R8","DOI":"10.1186\/gb-2006-7-1-r8","article-title":"A gold standard set of mechanistically diverse enzyme superfamilies","volume":"7","author":"Brown","year":"2006","journal-title":"Genome Biol."},{"key":"2020052504194914000_ref39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/ci00057a005","article-title":"SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules","volume":"28","author":"Weininger","year":"1988","journal-title":"J. Chem. Inf. Model."},{"key":"2020052504194914000_ref40","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1021\/bi052101l","article-title":"Leveraging enzyme structure-function relationships for functional inference and experimental design: the structure-function linkage database","volume":"45","author":"Pegg","year":"2006","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref41","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1021\/ci0502698","article-title":"Chemical markup, XML, and the world wide web. 6. CMLReact, an XML vocabulary for chemical reactions","volume":"46","author":"Holliday","year":"2006","journal-title":"J. Chem. Inf. Model."},{"key":"2020052504194914000_ref42","doi-asserted-by":"crossref","first-page":"30591","DOI":"10.1074\/jbc.272.49.30591","article-title":"Understanding enzyme superfamilies. Chemistry as the fundamental determinant in the evolution of new catalytic activities","volume":"272","author":"Babbitt","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2020052504194914000_ref43","doi-asserted-by":"crossref","first-page":"D434","DOI":"10.1093\/nar\/gkh119","article-title":"IntEnz, the integrated relational enzyme database","volume":"32","author":"Fleischmann","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2020052504194914000_ref44","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1021\/bi802277h","article-title":"Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymes","volume":"48","author":"Sakai","year":"2009","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref45","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.jmb.2006.06.049","article-title":"Evolutionary genomics of the HAD superfamily: understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes","volume":"361","author":"Burroughs","year":"2006","journal-title":"J. Mol. Biol."},{"key":"2020052504194914000_ref46","doi-asserted-by":"crossref","first-page":"e4345","DOI":"10.1371\/journal.pone.0004345","article-title":"Using sequence similarity networks for visualization of relationships across diverse protein superfamilies","volume":"4","author":"Atkinson","year":"2009","journal-title":"PLoS One"},{"key":"2020052504194914000_ref47","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1093\/bioinformatics\/btw096","article-title":"Reaction Decoder Tool (RDT): extracting features from chemical reactions","volume":"32","author":"Rahman","year":"2016","journal-title":"Bioinformatics"},{"key":"2020052504194914000_ref48","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jmb.2006.04.055","article-title":"Evolution of structure and function in the o-succinylbenzoate synthase\/N-acylamino acid racemase family of the enolase superfamily","volume":"360","author":"Glasner","year":"2006","journal-title":"J. Mol. Biol."},{"key":"2020052504194914000_ref49","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nchembio.2007.11","article-title":"Prediction and assignment of function for a divergent N-succinyl amino acid racemase","volume":"3","author":"Song","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"2020052504194914000_ref50","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1021\/bi034769a","article-title":"Evolutionary potential of (beta\/alpha)8-barrels: functional promiscuity produced by single substitutions in the enolase superfamily","volume":"42","author":"Schmidt","year":"2003","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref51","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jmb.2003.08.057","article-title":"How well is enzyme function conserved as a function of pairwise sequence identity?","volume":"333","author":"Tian","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2020052504194914000_ref52","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1006\/jmbi.2001.4513","article-title":"Evolution of function in protein superfamilies, from a structural perspective","volume":"307","author":"Todd","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2020052504194914000_ref53","doi-asserted-by":"crossref","first-page":"30221","DOI":"10.1074\/jbc.R114.569350","article-title":"New insights about enzyme evolution from large scale studies of sequence and structure relationships","volume":"289","author":"Brown","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2020052504194914000_ref54","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1128\/JB.183.8.2405-2410.2001","article-title":"Melamine deaminase and atrazine chlorohydrolase: 98 percent identical but functionally different","volume":"183","author":"Seffernick","year":"2001","journal-title":"J. Bacteriol."},{"key":"2020052504194914000_ref55","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-biochem-030409-143718","article-title":"Enzyme promiscuity: a mechanistic and evolutionary perspective","volume":"79","author":"Khersonsky","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"2020052504194914000_ref56","first-page":"193","article-title":"Mechanisms of protein evolution and their application to protein engineering","volume":"75","author":"Glasner","year":"2007","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"2020052504194914000_ref57","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbrc.2014.06.034","article-title":"Promiscuity of Exiguobacterium sp. AT1b o-succinylbenzoate synthase illustrates evolutionary transitions in the OSBS family","volume":"450","author":"Brizendine","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2020052504194914000_ref58","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/bi401176d","article-title":"Divergent evolution of ligand binding in the o-succinylbenzoate synthase family","volume":"52","author":"Odokonyero","year":"2013","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref59","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1021\/bi300753j","article-title":"Residues required for activity in Escherichia coli o-succinylbenzoate synthase (OSBS) are not conserved in all OSBS enzymes","volume":"51","author":"Zhu","year":"2012","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.abb.2004.07.034","article-title":"Divergent evolution in the enolase superfamily: the interplay of mechanism and specificity","volume":"433","author":"Gerlt","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"2020052504194914000_ref61","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1021\/bi501205e","article-title":"[FeFe]-hydrogenase maturation: insights into the role HydE plays in dithiomethylamine biosynthesis","volume":"54","author":"Betz","year":"2015","journal-title":"Biochemistry"},{"key":"2020052504194914000_ref62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1758-2946-1-12","article-title":"Small Molecule Subgraph Detector (SMSD) toolkit","volume":"1","author":"Rahman","year":"2009","journal-title":"J. Chem."},{"key":"2020052504194914000_ref63","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1021\/ci00062a008","article-title":"SMILES.2. Algorithm for generation of unique SMILES notation","volume":"29","author":"Weininger","year":"1989","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"2020052504194914000_ref64","first-page":"2012","article-title":"RDKit: open-source cheminformatics","volume":"3","author":"Landrum","year":"2006","journal-title":"Online"},{"key":"2020052504194914000_ref65","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1093\/bioinformatics\/bts532","article-title":"Pythoscape: a framework for generation of large protein similarity networks","volume":"28","author":"Barber","year":"2012","journal-title":"Bioinformatics"},{"key":"2020052504194914000_ref66","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"2020052504194914000_ref67","doi-asserted-by":"crossref","first-page":"D464","DOI":"10.1093\/nar\/gky1004","article-title":"RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy","volume":"47","author":"Burley","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020052504194914000_ref68","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1093\/nar\/gki524","article-title":"TM-align: a protein structure alignment algorithm based on the TM-score","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2020052504194914000_ref69","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nmeth.2803","article-title":"EC-BLAST: a tool to automatically search and compare enzyme reactions","volume":"11","author":"Rahman","year":"2014","journal-title":"Nat. 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