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Structural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies

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cris.lastimport.scopus2024-02-12T20:16:38Z
dc.abstract.enheD-2-hydroxyacid dehydrogenase (2HADH)family illustrates a complex evolutionary history with multiplelateral gene transfers and gene duplications and losses. As aresult, the exact functional annotation of individual memberscan be extrapolated to a very limited extent. Here, we revisethe previous simplified view on the classification of the2HADH family; specifically, we show that the previouslydelineated glyoxylate/hydroxypyruvate reductase (GHPR)subfamily consists of two evolutionary separated GHRA and GHRB subfamilies. We compare two representatives of thesesubfamilies fromSinorhizobium meliloti(SmGhrA andSmGhrB), employing a combination of biochemical, structural, andbioinformatics approaches. Our kinetic results show that both enzymes reduce several 2-ketocarboxylic acids with overlapping,but not equivalent, substrate preferences.SmGhrA andSmGhrB show highest activity with glyoxylate and hydroxypyruvate,respectively; in addition, onlySmGhrB reduces 2-keto-D-gluconate, and onlySmGhrA reduces pyruvate (with low efficiency). Wepresent nine crystal structures of both enzymes inapoforms and in complexes with cofactors and substrates/substrate analogues.In particular, we determined a crystal structure ofSmGhrB with 2-keto-D-gluconate, which is the biggest substrate cocrystallizedwith a 2HADH member. The structures reveal significant differences betweenSmGhrA andSmGhrB, both in the overallstructure and within the substrate-binding pocket, offering insight into the molecular basis for the observed substrate preferencesand subfamily differences. In addition, we provide an overview of all GHRA and GHRB structures complexed with a ligand in theactive site.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorHanding, Katarzyna B.
dc.contributor.authorShabalin, Ivan G.
dc.contributor.authorSroka, Piotr
dc.contributor.authorGórna, Maria
dc.contributor.authorGasiorowska, Olga
dc.contributor.authorMatelska, Dorota
dc.contributor.authorMinor, Wladek
dc.contributor.authorGinalski, Krzysztof
dc.contributor.authorWoźniak, Krzysztof
dc.contributor.authorKutner, Jan
dc.date.accessioned2024-01-26T08:21:18Z
dc.date.available2024-01-26T08:21:18Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number6
dc.description.volume57
dc.identifier.doi10.1021/ACS.BIOCHEM.7B01137
dc.identifier.issn0006-2960
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120877
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofBiochemistry
dc.relation.pages963-977
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleStructural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies
dc.typeJournalArticle
dspace.entity.typePublication