2dho
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Crystal structure of human IPP isomerase I in space group P212121
OverviewOverview
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.
About this StructureAbout this Structure
2DHO is a Single protein structure of sequence from Homo sapiens with MN, NA and CL as ligands. Active as Isopentenyl-diphosphate Delta-isomerase, with EC number 5.3.3.2 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of human IPP isomerase: new insights into the catalytic mechanism., Zhang C, Liu L, Xu H, Wei Z, Wang Y, Lin Y, Gong W, J Mol Biol. 2007 Mar 9;366(5):1437-46. Epub 2006 Nov 3. PMID:17137593
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