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Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase complexed with a mechanism‐based irreversible inhibitor
Author(s) -
Wouters J.,
Oudjama Y.,
Stalon V.,
Droogmans L.,
Poulter C.D.
Publication year - 2003
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10573
Subject(s) - isomerase , mutant , mechanism (biology) , chemistry , stereochemistry , mutation , biochemistry , enzyme , philosophy , gene , epistemology
Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase is a key enzyme in the biosynthesis of isoprenoids. The mechanism of the isomerization reaction involves protonation of the unactivated carbon‐carbon double bond in the substrate. Analysis of the 1.97 Å crystal structure of the inactive C67A mutant of E. coli isopentenyl diphosphate:dimethylallyl diphosphate isomerase complexed with the mechanism‐based inactivator 3,4‐epoxy‐3‐methyl‐1‐butyl diphosphate is in agreement with an isomerization mechanism involving Glu 116, Tyr 104, and Cys 67. In particular, the results are consistent with a mechanism where Glu116 is involved in the protonation step and Cys67 in the elimination step. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.