IMP dehydrogenase: structural schizophrenia and an unusual base

Curr Opin Chem Biol. 2006 Oct;10(5):520-5. doi: 10.1016/j.cbpa.2006.08.005. Epub 2006 Aug 17.

Abstract

Textbooks describe enzymes as relatively rigid templates for the transition state of a chemical reaction, and indeed an enzyme such as chymotrypsin, which catalyzes a relatively simple hydrolysis reaction, is reasonably well described by this model. Inosine monophosphate dehydrogenase (IMPDH) undergoes a remarkable array of conformational transitions in the course of a complicated catalytic cycle, offering a dramatic counterexample to this view. IMPDH displays several other unusual mechanistic features, including an Arg residue that may act as a general base catalyst and a dynamic monovalent cation site. Further, IMPDH appears to be involved in 'moon-lighting' functions that may require additional conformational states. How the balance between conformational states is maintained and how the various conformational states interconvert is only beginning to be understood.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Catalysis
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Hydrogen-Ion Concentration
  • IMP Dehydrogenase / antagonists & inhibitors
  • IMP Dehydrogenase / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acids / chemistry*
  • Protein Conformation

Substances

  • Enzyme Inhibitors
  • Nucleic Acids
  • IMP Dehydrogenase