IMP dehydrogenase: structural schizophrenia and an unusual base.
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.
Hedstrom
Lizbeth
L
Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA. hedstrom@brandeis.edu
Gan
Lu
L
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry*; D011487:Protein Conformation
D004791:Enzyme Inhibitors; D009696:Nucleic Acids; D007168:IMP Dehydrogenase