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Classification, substrate specificity and structural features of D-2-hydroxyacid dehydrogenases: 2HADH knowledgebase

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dc.abstract.enBackground: The family of D-isomer specific 2-hydroxyacid dehydrogenases (2HADHs) contains a wide range of oxidoreductases with various metabolic roles as well as biotechnological applications. Despite a vast amount of biochemical and structural data for various representatives of the family, the long and complex evolution and broad sequence diversity hinder functional annotations for uncharacterized members. Results: We report an in-depth phylogenetic analysis, followed by mapping of available biochemical and structural data on the reconstructed phylogenetic tree. The analysis suggests that some subfamilies comprising enzymes with similar yet broad substrate specificity profiles diverged early in the evolution of 2HADHs. Based on the phylogenetic tree, we present a revised classification of the family that comprises 22 subfamilies, including 13 new subfamilies not studied biochemically. We summarize characteristics of the nine biochemically studied subfamilies by aggregating all available sequence, biochemical, and structural data, providing comprehensive descriptions of the active site, cofactor-binding residues, and potential roles of specific structural regions in substrate recognition. In addition, we concisely present our analysis as an online 2HADH enzymes knowledgebase. Conclusions: The knowledgebase enables navigation over the 2HADHs classification, search through collected data, and functional predictions of uncharacterized 2HADHs. Future characterization of the new subfamilies may result in discoveries of enzymes with novel metabolic roles and with properties beneficial for biotechnological applications.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorShabalin, Ivan G.
dc.contributor.authorMinor, Wladek
dc.contributor.authorJabłońska, Jagoda
dc.contributor.authorDomagalski, Marcin J.
dc.contributor.authorMatelska, Dorota
dc.contributor.authorGinalski, Krzysztof
dc.contributor.authorKutner, Jan
dc.date.accessioned2024-01-24T19:25:06Z
dc.date.available2024-01-24T19:25:06Z
dc.date.copyright2018-12-22
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume18
dc.identifier.doi10.1186/S12862-018-1309-8
dc.identifier.issn1471-2148
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/103122
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBMC Evolutionary Biology
dc.relation.pagesart.no. 199
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enD-isomer specific 2-hydroxyacid dehydrogenases
dc.subject.enMolecular evolution
dc.subject.enSequence-structure-function relationship
dc.subject.enSubstrate promiscuity
dc.subject.enSubstrate specificity
dc.titleClassification, substrate specificity and structural features of D-2-hydroxyacid dehydrogenases: 2HADH knowledgebase
dc.typeJournalArticle
dspace.entity.typePublication