1PN2

Crystal structure analysis of the selenomethionine labelled 2-enoyl-CoA hydratase 2 domain of Candida tropicalis multifunctional enzyme type 2

1PN2 の概要

• エントリーDOI: 10.2210/pdb1pn2/pdb
• 関連するPDBエントリー: 1PN4
• 分子名称: Peroxisomal hydratase-dehydrogenase-epimerase, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: hot-dog fold, hydratase 2 motif, lyase
• 由来する生物種: Candida tropicalis
• 細胞内の位置: Peroxisome: P22414
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 126687.63

構造登録者

Koski, M.K.,Haapalainen, A.M.,Hiltunen, J.K.,Glumoff, T. (登録日: 2003-06-12, 公開日: 2004-04-13, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)