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Human isopentenyl diphophate isomerase complexed with substrate analog
Structural highlights
FunctionIDI1_HUMAN Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIsopentenyl diphosphate isomerase catalyses a crucial activation step in the biosynthesis of isoprenoids, one of the most ancient and diverse classes of natural products. This enzyme is responsible for an unusual isomerization of the inactive carbon-carbon double bond of isopentenyl diphosphate (IPP) to create its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP). Here we report the crystal structure of human IPP isomerase at 1.7 A resolution and the complex structure with its native substrate at 1.9 A resolution. These structures reveal a mechanism wherein interconversion is catalyzed by a stereoselective antarafacial [1.3] transposition of a proton involving the indispensable residues Cys87, Glu149, Trp197 and Tyr137. A newly identified alternative conformation of Cys87 driven by Trp197 and the selectivity of different metal ions located in the active site provide further insight into the catalytic mechanism. Comparison with Escherichia coli IPP isomerase reveals a novel substrate entrance in human IPP isomerase. The crystal structure of human isopentenyl diphosphate isomerase at 1.7 A resolution reveals its catalytic mechanism in isoprenoid biosynthesis.,Zheng W, Sun F, Bartlam M, Li X, Li R, Rao Z J Mol Biol. 2007 Mar 9;366(5):1447-58. Epub 2006 Dec 24. PMID:17250851[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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