5OMO

CRYSTAL STRUCTURE OF RAT PEROXISOMAL MULTIFUNCTIONAL ENZYME TYPE-1 (RPMFE1) COMPLEXED WITH WITH 3S-HYDROXY-DECANOYL-COA AND 3-KETO-DECANOYL-COA

Replaces:  5AAJ

Summary for 5OMO

• Entry DOI: 10.2210/pdb5omo/pdb
• Related: 5MGB
• Descriptor: Peroxisomal bifunctional enzyme, SULFATE ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: oxidoreductase, 3s-hydroxy-decanoyl-coa, 3-keto-decanoyl-coa, mfe1, beta-oxidation, fatty acid, crotonase, 3-hydroxyacyl-coa- dehydrogenase, hydratase
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 165518.63

Authors

Kasaragod, P.,Kiema, T.-R.,Schmitz, W.,Hiltunen, J.K.,Wierenga, R.K. (deposition date: 2017-08-01, release date: 2017-09-06, Last modification date: 2025-03-19)

Primary citation

Sridhar, S.,Schmitz, W.,Hiltunen, J.K.,Venkatesan, R.,Bergmann, U.,Kiema, T.R.,Wierenga, R.K.
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.
Acta Crystallogr D Struct Biol, 76:1256-1269, 2020

PubMed Abstract: The peroxisomal multifunctional enzyme type 1 (MFE1) catalyzes two successive reactions in the β-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 Å 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.

PubMed: 33263331
DOI: 10.1107/S2059798320013819

Experimental method

X-RAY DIFFRACTION (2.49 Å)