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1pn4

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1pn4, resolution 2.35Å

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Crystal structure of 2-enoyl-CoA hydratase 2 domain of Candida tropicalis multifunctional enzyme type 2 complexed with (3R)-hydroxydecanoyl-CoA.

Overview

2-Enoyl-CoA hydratase 2, a part from multifunctional enzyme type 2, hydrates trans-2-enoyl-CoA to 3-hydroxyacyl-CoA in the, (3R)-hydroxy-dependent route of peroxisomal beta-oxidation of fatty acids., Unliganded and (3R)-hydroxydecanoyl coenzyme A-complexed crystal, structures of 2-enoyl-CoA hydratase 2 from Candida tropicalis, multifunctional enzyme type 2 were solved to 1.95- and 2.35-A resolution, respectively. 2-Enoyl-CoA hydratase 2 is a dimeric, alpha+beta protein, with a novel quaternary structure. The overall structure of the two-domain, subunit of eukaryotic 2-enoyl-CoA hydratase 2 resembles the homodimeric, hot dog fold structures of prokaryotic (R)-specific 2-enoyl-CoA hydratase, and beta-hydroxydecanoyl thiol ester dehydrase. Importantly, though, the, eukaryotic hydratase 2 has a complete hot dog fold only in its C-domain, whereas the N-domain lacks a long central alpha-helix, thus creating space, for bulkier substrates in the binding pocket and explaining the observed, difference in substrate preference between eukaryotic and prokaryotic, enzymes. Although the N- and C-domains have an identity of <10% at the, amino acid level, they share a 50% identity at the nucleotide level and, fold similarly. We suggest that a subunit of 2-enoyl-CoA hydratase 2 has, evolved via a gene duplication with the concomitant loss of one catalytic, site. The hydrogen bonding network of the active site of 2-enoyl-CoA, hydratase 2 resembles the active site geometry of mitochondrial, (S)-specific 2-enoyl-CoA hydratase 1, although in a mirror image fashion., This arrangement allows the reaction to occur by similar mechanism, supported by mutagenesis and mechanistic studies, although via reciprocal, stereochemistry.

About this Structure

1PN4 is a Single protein structure of sequence from Candida tropicalis with HDC and EDO as ligands. Full crystallographic information is available from OCA.

Reference

A two-domain structure of one subunit explains unique features of eukaryotic hydratase 2., Koski MK, Haapalainen AM, Hiltunen JK, Glumoff T, J Biol Chem. 2004 Jun 4;279(23):24666-72. Epub 2004 Mar 29. PMID:15051722

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