2ICJ

The crystal structure of human isopentenyl diphophate isomerase

Summary for 2ICJ

• Entry DOI: 10.2210/pdb2icj/pdb
• Related: 2ICK
• Descriptor: Isopentenyl-diphosphate delta isomerase, MAGNESIUM ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: human isopentenyl diphophate isomerase, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 27018.20

Authors

Zheng, W.,Bartlam, M.,Rao, Z. (deposition date: 2006-09-12, release date: 2007-03-20, Last modification date: 2024-03-13)

Primary citation

Zheng, W.,Sun, F.,Bartlam, M.,Li, X.,Li, R.,Rao, Z.
The crystal structure of human isopentenyl diphosphate isomerase at 1.7 A resolution reveals its catalytic mechanism in isoprenoid biosynthesis
J.Mol.Biol., 366:1447-1458, 2007

PubMed Abstract: Isopentenyl 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.

PubMed: 17250851
DOI: 10.1016/j.jmb.2006.12.055

Experimental method

X-RAY DIFFRACTION (1.7 Å)