2GCI

The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an asparte/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety

2GCI の概要

• エントリーDOI: 10.2210/pdb2gci/pdb
• 関連するPDBエントリー: 1X74 2GCE 2GD0 2GD2 2GD6
• 分子名称: probable alpha-methylacyl-CoA racemase MCR, (R)-2-METHYLMYRISTOYL-COENZYME A, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: alpha-methylacyl-coa racemase, racemase, coa transferase, proton transfer, coenzyme a, isomerase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159411.43

構造登録者

Bhaumik, P.,Wierenga, R.K. (登録日: 2006-03-14, 公開日: 2007-02-20, 最終更新日: 2023-10-25)

主引用文献

Bhaumik, P.,Schmitz, W.,Hassinen, A.,Hiltunen, J.K.,Conzelmann, E.,Wierenga, R.K.
The Catalysis of the 1,1-Proton Transfer by alpha-Methyl-acyl-CoA Racemase Is Coupled to a Movement of the Fatty Acyl Moiety Over a Hydrophobic, Methionine-rich Surface
J.Mol.Biol., 367:1145-1161, 2007

PubMed Abstract: Alpha-methylacyl-CoA racemases are essential enzymes for branched-chain fatty acid metabolism. Their reaction mechanism and the structural basis of their wide substrate specificity are poorly understood. High-resolution crystal structures of Mycobacterium tuberculosis alpha-methylacyl-CoA racemase (MCR) complexed with substrate molecules show the active site geometry required for catalysis of the interconversion of (2S) and (2R)-methylacyl-CoA. The thioester oxygen atom and the 2-methyl group are in a cis-conformation with respect to each other. The thioester oxygen atom fits into an oxyanion hole and the 2-methyl group points into a hydrophobic pocket. The active site geometry agrees with a 1,1-proton transfer mechanism in which the acid/base-pair residues are His126 and Asp156. The structures of the complexes indicate that the acyl chains of the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively. A unique feature of MCR is a large number of methionine residues in the acyl binding region, located between the S-pocket and the R-pocket. It appears that the (S) to (R) interconversion of the 2-methylacyl chiral center is coupled to a movement of the acyl group over this hydrophobic, methionine-rich surface, when moving from its S-pocket to its R-pocket, whereas the 2-methyl moiety and the CoA group remain fixed in their respective pockets.

PubMed: 17320106
DOI: 10.1016/j.jmb.2007.01.062

実験手法

X-RAY DIFFRACTION (1.6 Å)