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Crystallographic bi...
Crystallographic binding studies of rat peroxisomal multifunctional enzyme type 1 with 3-ketodecanoyl-CoA : capturing active and inactive states of its hydratase and dehydrogenase catalytic sites
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- Sridhar, Shruthi (author)
- Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland;Biocenter Oulu, University of Oulu, Oulu, Finland
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Schmitz, Werner (author)
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Hiltunen, J. Kalervo (author)
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Venkatesan, Rajaram (author)
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Bergmann, Ulrich (author)
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Kiema, Tiila-Riikka (author)
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Wierenga, Rikkert K. (author)
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(creator_code:org_t)
- 2020-11-24
- 2020
- English.
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In: Acta Crystallographica Section D. - : International Union of Crystallography (IUCr). - 2059-7983. ; 76:12, s. 1256-1269
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The peroxisomal multifunctional enzyme type 1 (MFE1) catalyzes two successive reactions in the beta-oxidation cycle: the 2E-enoyl-CoA hydratase (ECH) and NAD(+)-dependent 3S-hydroxyacyl-CoA dehydrogenase (HAD) reactions. MFE1 is a monomeric enzyme that has five domains. The N-terminal part (domains A and B) adopts the crotonase fold and the C-terminal part (domains C, D and E) adopts the HAD fold. A new crystal form of MFE1 has captured a conformation in which both active sites are noncompetent. This structure, at 1.7 angstrom resolution, shows the importance of the interactions between Phe272 in domain B (the linker helix; helix H10 of the crotonase fold) and the beginning of loop 2 (of the crotonase fold) in stabilizing the competent ECH active-site geometry. In addition, protein crystallographic binding studies using optimized crystal-treatment protocols have captured a structure with both the 3-ketodecanoyl-CoA product and NAD(+) bound in the HAD active site, showing the interactions between 3-ketodecanoyl-CoA and residues of the C, D and E domains. Structural comparisons show the importance of domain movements, in particular of the C domain with respect to the D/E domains and of the A domain with respect to the HAD part. These comparisons suggest that the N-terminal part of the linker helix, which interacts tightly with domains A and E, functions as a hinge region for movement of the A domain with respect to the HAD part.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- peroxisomal multifunctional enzyme type 1
- Rossmann fold
- reaction mechanism
- closed active site
- fatty-acid oxidation
- conformational flexibility.
- Biology with specialization in Structural Biology
- Biologi med inriktning mot strukturbiologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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