2VCY

Crystal Structure of 2-Enoyl Thioester Reductase of Human FAS II

2VCY の概要

• エントリーDOI: 10.2210/pdb2vcy/pdb
• 関連するPDBエントリー: 1ZSY
• 分子名称: TRANS-2-ENOYL-COA REDUCTASE, SULFATE ION (3 entities in total)
• 機能のキーワード: nadp, polymorphism, mitochondrion, oxidoreductase, fatty acid biosynthesis, enoyl thioester reductase, lipid synthesis, transit peptide
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75500.41

構造登録者

Haapalainen, A.M.,Pudas, R.,Smart, O.S.,Wierenga, R.K. (登録日: 2007-09-28, 公開日: 2008-06-03, 最終更新日: 2023-12-13)

主引用文献

Chen, Z.J.,Pudas, R.,Sharma, S.,Smart, O.S.,Juffer, A.H.,Hiltunen, J.K.,Wierenga, R.K.,Haapalainen, A.M.
Structural Enzymological Studies of 2-Enoyl Thioester Reductase of the Human Mitochondrial Fas II Pathway: New Insights Into its Substrate Recognition Properties.
J.Mol.Biol., 379:830-, 2008

PubMed Abstract: Structural and kinetic properties of the human 2-enoyl thioester reductase [mitochondrial enoyl-coenzyme A reductase (MECR)/ETR1] of the mitochondrial fatty acid synthesis (FAS) II pathway have been determined. The crystal structure of this dimeric enzyme (at 2.4 A resolution) suggests that the binding site for the recognition helix of the acyl carrier protein is in a groove between the two adjacent monomers. This groove is connected via the pantetheine binding cleft to the active site. The modeled mode of NADPH binding, using molecular dynamics calculations, suggests that Tyr94 and Trp311 are critical for catalysis, which is supported by enzyme kinetic data. A deep, water-filled pocket, shaped by hydrophobic and polar residues and extending away from the catalytic site, was recognized. This pocket can accommodate a fatty acyl tail of up to 16 carbons. Mutagenesis of the residues near the end of this pocket confirms the importance of this region for the binding of substrate molecules with long fatty acyl tails. Furthermore, the kinetic analysis of the wild-type MECR/ETR1 shows a bimodal distribution of catalytic efficiencies, in agreement with the notion that two major products are generated by the mitochondrial FAS II pathway.

PubMed: 18479707
DOI: 10.1016/J.JMB.2008.04.041

実験手法

X-RAY DIFFRACTION (2.41 Å)