1q54
STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH THE BROMOHYDRINE OF IPP
OverviewOverview
We have obtained the three-dimensional X-ray crystallographic structure of a C67A mutant Escherichia coli isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase (EC 5.3.3.2) complexed with the bromohydrin of isopentenylpyrophosphate, at 1.93 A resolution. The overall backbone fold is very similar to that obtained previously for the wild-type enzyme in the presence of a divalent metal cation (Mn2+ or Mg2+). However, in the new structure, there are two metal binding sites, not just one. The first metal binding site is occupied by Mn2+, coordinated to three histidine and two glutamate residues, while the second is occupied by Mg2+, coordinated to two bromohydrin-ligand phosphate oxygens, the carbonyl oxygen of A67, a carboxyl oxygen of E87, and two water molecules. The C3 hydroxyl group of the bromohydrin inhibitor is involved in a short hydrogen bond to the carboxyl group of E116, one of the two Mn-bound glutamates. The structure obtained is consistent with a mechanism of action of the enzyme in which the carboxyl group of E116 protonates the double bond in isopentenylpyrophosphate, forming a carbocation, followed by removal of a C2 proton by the thiolate of C67, in the wild-type enzyme. The inhibition of the enzyme by a wide variety of other potent inhibitors is also readily explained on the basis of the bromohydrin inhibitor structure.
About this StructureAbout this Structure
1Q54 is a Single protein structure of sequence from Escherichia coli. This structure supersedes the now removed PDB entry 1n2u. Full crystallographic information is available from OCA.
ReferenceReference
Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase., Wouters J, Oudjama Y, Ghosh S, Stalon V, Droogmans L, Oldfield E, J Am Chem Soc. 2003 Mar 19;125(11):3198-9. PMID:12630859 Page seeded by OCA on Sat May 3 05:52:29 2008