2DHO

Crystal structure of human IPP isomerase I in space group P212121

2DHO の概要

• エントリーDOI: 10.2210/pdb2dho/pdb
• 関連するPDBエントリー: 2EWQ
• 分子名称: Isopentenyl-diphosphate delta-isomerase 1, MANGANESE (II) ION, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: alpha/beta protein, isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Peroxisome: Q13907
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28214.35

構造登録者

Zhang, C.,Wei, Z.,Gong, W. (登録日: 2006-03-24, 公開日: 2007-06-05, 最終更新日: 2021-11-10)

主引用文献

Zhang, C.,Liu, L.,Xu, H.,Wei, Z.,Wang, Y.,Lin, Y.,Gong, W.
Crystal structures of human IPP isomerase: new insights into the catalytic mechanism
J.Mol.Biol., 366:1437-1446, 2007

PubMed Abstract: Type I isopentenyl diphosphate (IPP): dimethylally diphosphate (DMAPP) isomerase is an essential enzyme in human isoprenoid biosynthetic pathway. It catalyzes isomerization of the carbon-carbon double bonds in IPP and DMAPP, which are the basic building blocks for the subsequent biosynthesis. We have determined two crystal structures of human IPP isomerase I (hIPPI) under different crystallization conditions. High similarity between structures of human and Escherichia coli IPP isomerases proves the conserved catalytic mechanism. Unexpectedly, one of the hIPPI structures contains a natural substrate analog ethanol amine pyrophosphate (EAPP). Based on this structure, a water molecule is proposed to be the direct proton donor for IPP and different conformations of IPP and DMAPP bound in the enzyme are also proposed. In addition, structures of human IPPI show a flexible N-terminal alpha-helix covering the active pocket and blocking the entrance, which is absent in E. coli IPPI. Besides, the active site conformation is not the same in the two hIPPI structures. Such difference leads to a hypothesis that substrate binding induces conformational change in the active site. The inhibition mechanism of high Mn(2+) concentrations is also discussed.

PubMed: 17137593
DOI: 10.1016/j.jmb.2006.10.092

実験手法

X-RAY DIFFRACTION (1.6 Å)