1PN4

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

Summary for 1PN4

• Entry DOI: 10.2210/pdb1pn4/pdb
• Related: 1PN2
• Descriptor: Peroxisomal hydratase-dehydrogenase-epimerase, 3R-HYDROXYDECANOYL-COENZYME A, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: hot-dog fold, hydratase 2 motif, oxyanion hole, enzyme-product complex, lyase
• Biological source: Candida tropicalis
• Total number of polymer chains: 4
• Total formula weight: 128648.54

Authors

Koski, M.K.,Haapalainen, A.M.,Hiltunen, J.K.,Glumoff, T. (deposition date: 2003-06-12, release date: 2004-04-13, Last modification date: 2023-08-16)

Primary citation

Koski, M.K.,Haapalainen, A.M.,Hiltunen, J.K.,Glumoff, T.
A Two-domain Structure of One Subunit Explains Unique Features of Eukaryotic Hydratase 2.
J.Biol.Chem., 279:24666-24672, 2004

PubMed Abstract: 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.

PubMed: 15051722
DOI: 10.1074/jbc.M400293200

Experimental method

X-RAY DIFFRACTION (2.35 Å)