1Q54

STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH THE BROMOHYDRINE OF IPP

Replaces:  1N2U

Summary for 1Q54

• Entry DOI: 10.2210/pdb1q54/pdb
• Related: 1HX3 1HZT
• Descriptor: ISOPENTENYL DIPHOSPHATE DELTA-ISOMERASE, MANGANESE (II) ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: complex, isomerase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: Q46822
• Total number of polymer chains: 2
• Total formula weight: 42069.14

Authors

Wouters, J.,Oudjama, Y.,Ghosh, S.,Stalon, V.,Droogmans, L. (deposition date: 2003-08-06, release date: 2003-08-26, Last modification date: 2023-08-16)

Primary citation

Wouters, J.,Oudjama, Y.,Ghosh, S.,Stalon, V.,Droogmans, L.,Oldfield, E.
Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase.
J.Am.Chem.Soc., 125:3198-3199, 2003

PubMed Abstract: 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.

PubMed: 12630859
DOI: 10.1021/ja029171p

Experimental method

X-RAY DIFFRACTION (1.93 Å)