2WYA

CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL- COENZYME A SYNTHASE 2 (HMGCS2)

「2V4W」から置き換えられました

2WYA の概要

• エントリーDOI: 10.2210/pdb2wya/pdb
• 分子名称: HYDROXYMETHYLGLUTARYL-COA SYNTHASE, MITOCHONDRIAL, 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: steroid biosynthesis, cholesterol biosynthesis, mitochondria, mitochondrion, phosphoprotein, melavonate pathway, sterol biosynthesis, thiolase, acetylation, transferase, lipid synthesis, transit peptide, disease mutation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion: P54868
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 208982.43

構造登録者

Yue, W.W.,Shafqat, N.,Savitsky, P.,Roos, A.K.,Cooper, C.,Murray, J.W.,von Delft, F.,Arrowsmith, C.,Wikstrom, M.,Edwards, A.,Bountra, C.,Oppermann, U. (登録日: 2009-11-13, 公開日: 2009-11-24, 最終更新日: 2024-11-20)

主引用文献

Shafqat, N.,Turnbull, A.,Zschocke, J.,Oppermann, U.,Yue, W.W.
Crystal Structures of Human Hmg-Coa Synthase Isoforms Provide Insights Into Inherited Ketogenesis Disorders and Inhibitor Design.
J.Mol.Biol., 398:497-, 2010

PubMed Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl CoA. It is ubiquitous across the phylogenetic tree and is broadly classified into three classes. The prokaryotic isoform is essential in Gram-positive bacteria for isoprenoid synthesis via the mevalonate pathway. The eukaryotic cytosolic isoform also participates in the mevalonate pathway but its end product is cholesterol. Mammals also contain a mitochondrial isoform; its deficiency results in an inherited disorder of ketone body formation. Here, we report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes. Our data represent the first structures solved for human HMGCS and the mitochondrial isoform, allowing for the first time structural comparison among the three isoforms. This serves as a starting point for the development of isoform-specific inhibitors that have potential cholesterol-reducing and antibiotic applications. In addition, missense mutations that cause mitochondrial HMGCS deficiency have been mapped onto the hHMGCS2 structure to rationalize the structural basis for the disease pathology.

PubMed: 20346956
DOI: 10.1016/J.JMB.2010.03.034

実験手法

X-RAY DIFFRACTION (1.7 Å)