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Crystal structure of an apo 7α-hydroxysteroid dehydrogenase reveals key structural changes induced by substrate and co-factor binding

Cited 2 time in wos
Cited 2 time in scopus

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dc.contributor.authorKim, Ki-Hwa-
dc.contributor.authorLee, Chang Woo-
dc.contributor.authorPardhe, Bashu Dev-
dc.contributor.authorHwang, Jisub-
dc.contributor.authorDo, Hackwon-
dc.contributor.authorLee, Yung Mi-
dc.contributor.authorLee, Jun Hyuck-
dc.contributor.authorOh, Tae-Jin-
dc.date.accessioned2021-11-26T07:52:16Z-
dc.date.available2021-11-26T07:52:16Z-
dc.date.issued2021-09-
dc.identifier.urihttps://repository.kopri.re.kr/handle/201206/12981-
dc.description.abstract7α-Hydroxysteroid dehydrogenase (7α-HSDH) catalyzes the dehydrogenation of a hydroxyl group at the 7α position in steroid substrates using NAD+ or NADP+ as a co-factor. Although studies have determined the binary and ternary complex structures, detailed structural changes induced by ligand and co-factor binding remain unclear, because ligand-free structures are not yet available. Here, we present the crystal structure of apo 7α-HSDH from Escherichia coli (Eco-7α-HSDH) at 2.7 A resolution. We found that the apo form undergoes substantial conformational changes in the β4-α4 loop, α7-α8 helices, and C-terminus loop among the four subunits comprising the tetramer. Furthermore, a comparison of the apo structure with the binary (NAD+)-complex and ternary (NADH and 7-oxoglycochenodeoxycholic acid)-complex Eco-7α-HSDH structures revealed that only the ternary-complex structure has a fully closed conformation, whereas the binary-complex and apo structures have a semi-closed or open conformation. This open-to-closed transition forces several catalytically important residues (S146, Y159, and K163) into correct positions for catalysis. To confirm the catalytic activity, we used alcohol dehydrogenase for NAD+ regeneration to allow efficient conversion of chenodeoxycholic acid to 7-ketolithocholic acid by Eco-7α-HSDH. These findings demonstrate that apo Eco-7α-HSDH exhibits intrinsically flexible characteristics with an open conformation. This structural information provides novel insight into the 7α-HSDH reaction mechanism.en_US
dc.languageEnglishen_US
dc.language.isoenen_US
dc.subjectBiochemistry & Molecular Biologyen_US
dc.subjectEndocrinology & Metabolismen_US
dc.subject.classification해당사항없음en_US
dc.titleCrystal structure of an apo 7α-hydroxysteroid dehydrogenase reveals key structural changes induced by substrate and co-factor bindingen_US
dc.title.alternative7α-hydroxysteroid dehydrogenase 효소의 구조분석을 통한 조효소와 기질 결합에 의한 구조변화 연구en_US
dc.typeArticleen_US
dc.identifier.bibliographicCitationKim, Ki-Hwa, et al. 2021. "Crystal structure of an apo 7α-hydroxysteroid dehydrogenase reveals key structural changes induced by substrate and co-factor binding". <em>JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY</em>, 212: 1-8.-
dc.citation.titleJOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGYen_US
dc.citation.volume212en_US
dc.identifier.doi10.1016/j.jsbmb.2021.105945-
dc.citation.startPage1en_US
dc.citation.endPage8en_US
dc.description.articleClassificationSCIE-
dc.description.jcrRateJCR 2019:31.469en_US
dc.subject.keywordCrystal structureen_US
dc.subject.keywordConformational changeen_US
dc.subject.keyword7 alpha-hydroxysteroid dehydrogenaseen_US
dc.subject.keywordX-ray crystallographyen_US
dc.identifier.localId2021-0120-
dc.identifier.scopusid2-s2.0-85110463826-
dc.identifier.wosid000688410500013-
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