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Critical residues f...
Critical residues for structure and catalysis in short-chain dehydrogenases/reductases
- Article/chapterEnglish2002
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LIBRIS-ID:oai:DiVA.org:sh-15793
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https://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-15793URI
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https://doi.org/10.1074/jbc.M202160200DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1938030URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Short-chain dehydrogenases/reductases form a large, evolutionarily old family of NAD(P)(H)-dependent enzymes with over 60 genes found in the human genome. Despite low levels of sequence identity (often 10-30%), the three-dimensional structures display a highly similar alpha/beta folding pattern. We have analyzed the role of several conserved residues regarding folding, stability, steady-state kinetics, and coenzyme binding using bacterial 3beta/17beta-hydroxysteroid dehydrogenase and selected mutants. Structure determination of the wildtype enzyme at 1.2-Angstrom resolution by x-ray crystallography and docking analysis was used to interpret the biochemical data. Enzyme kinetic data from mutagenetic replacements emphasize the critical role of residues Thr-12, Asp-60, Asn-86, Asn-87, and Ala-88 in coenzyme binding and catalysis. The data also demonstrate essential interactions of Asn-111 with active site residues. A general role of its side chain interactions for maintenance of the active site configuration to build up a proton relay system is proposed. This extends the previously recognized catalytic triad of Ser-Tyr-Lys residues to form a tetrad of Asn-Ser-Tyr-Lys in the majority of characterized short-chain dehydrogenases/reductase enzymes.
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Berndt, Kurt DKarolinska Institutet,Södertörns högskola,Avdelning Naturvetenskap,Karolinska Intitute(Swepub:sh)SHKTBT
(author)
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Benach, J
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Knapp, S
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Prozorovski, T
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Nordling, E
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Ladenstein, RKarolinska Institutet
(author)
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Jörnvall, HKarolinska Institutet
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Oppermann, U
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Södertörns högskolaAvdelning Naturvetenskap
(creator_code:org_t)
Related titles
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In:Journal of Biological Chemistry277:28, s. 25677-256840021-92581083-351X
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