6Z5F

CRYSTAL STRUCTURE OF RAT PEROXISOMAL MULTIFUNCTIONAL ENZYME TYPE-1 (RPMFE1) COMPLEXED WITH 3-KETODECANOYL-COA AND OXIDISED NICOTINAMIDE ADENINE DINUCLEOTIDE

This is a non-PDB format compatible entry.

Summary for 6Z5F

• Entry DOI: 10.2210/pdb6z5f/pdb
• Related: 2X58
• Descriptor: Peroxisomal bifunctional enzyme, 3-KETO-DECANOYL-COA, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (6 entities in total)
• Functional Keywords: 3-ketodecanoyl-coa, beta-oxidation, peroxisome, oxidoreductase
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 166373.17

Authors

Wierenga, R.K.,Sridhar, S.,Kiema, T.R. (deposition date: 2020-05-26, release date: 2020-12-09, Last modification date: 2024-01-24)

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 (2.25 Å)