3C5E

Crystal structure of human acyl-CoA synthetase medium-chain family member 2A (L64P mutation) in complex with ATP

3C5E の概要

• エントリーDOI: 10.2210/pdb3c5e/pdb
• 関連するPDBエントリー: 3B7W
• 分子名称: Acyl-coenzyme A synthetase ACSM2A, mitochondrial precursor, MAGNESIUM ION, CHLORIDE ION, ... (8 entities in total)
• 機能のキーワード: middle-chain acyl-coa synthetase, xenobiotic/medium-chain fatty acid-coa ligase, structural genomics consortium, sgc, atp-binding, fatty acid metabolism, lipid metabolism, magnesium, metal-binding, mitochondrion, nucleotide-binding polymorphism, transit peptide, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix : Q08AH3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64175.50

構造登録者

Pilka, E.S.,Kochan, G.T.,Bhatia, C.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Oppermann, U.,Structural Genomics Consortium (SGC) (登録日: 2008-01-31, 公開日: 2008-02-26, 最終更新日: 2023-08-30)

主引用文献

Kochan, G.,Pilka, E.S.,von Delft, F.,Oppermann, U.,Yue, W.W.
Structural snapshots for the conformation-dependent catalysis by human medium-chain acyl-coenzyme A synthetase ACSM2A.
J.Mol.Biol., 388:997-1008, 2009

PubMed Abstract: Acyl-CoA synthetases belong to the superfamily of adenylate-forming enzymes, and catalyze the two-step activation of fatty acids or carboxylate-containing xenobiotics. The carboxylate substrate first reacts with ATP to form an acyl-adenylate intermediate, which then reacts with CoA to produce an acyl-CoA ester. Here, we report the first crystal structure of a medium-chain acyl-CoA synthetase ACSM2A, in a series of substrate/product/cofactor complexes central to the catalytic mechanism. We observed a substantial rearrangement between the N- and C-terminal domains, driven purely by the identity of the bound ligand in the active site. Our structures allowed us to identify the presence or absence of the ATP pyrophosphates as the conformational switch, and elucidated new mechanistic details, including the role of invariant Lys557 and a divalent magnesium ion in coordinating the ATP pyrophosphates, as well as the involvement of a Gly-rich P-loop and the conserved Arg472-Glu365 salt bridge in the domain rearrangement.

PubMed: 19345228
DOI: 10.1016/j.jmb.2009.03.064

実験手法

X-RAY DIFFRACTION (1.6 Å)