Study of IspH, a key enzyme in the methylerythritol phosphate pathway using fluoro-substituted substrate analogues

Org Lett. 2011 Nov 4;13(21):5912-5. doi: 10.1021/ol202559r. Epub 2011 Oct 7.

Abstract

IspH, a [4Fe-4S]-cluster-containing enzyme, catalyzes the reductive dehydroxylation of 4-hydroxy-3-methyl-butenyl diphosphate (HMBPP) to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the methylerythritol phosphate pathway. Studies of IspH using fluoro-substituted substrate analogues to dissect the contributions of several factors to IspH catalysis, including the coordination of the HMBPP C(4)-OH group to the iron-sulfur cluster, the H-bonding network in the active site, and the electronic properties of the substrates, are reported.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / metabolism*
  • Biocatalysis
  • Erythritol / chemistry*
  • Erythritol / metabolism
  • Fluorine Compounds / chemistry*
  • Fluorine Compounds / metabolism
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Substrate Specificity
  • Sugar Phosphates / chemistry*
  • Sugar Phosphates / metabolism

Substances

  • Fluorine Compounds
  • Sugar Phosphates
  • Alkyl and Aryl Transferases
  • Erythritol