Valentina Di Francescovdifrancesco@niaid.nih.gov
Purine nucleotides play a key role in synthesis of DNA, RNA and ATP supply in all living organisms. Many pathogens are deficient in de novo synthesis of the purine nucleotides, and therefore must rely on salvage pathway.
The differences in purine base metabolism between pathogenic bacteria and their mammalian hosts have stimulated considerable interest in the salvage pathway enzymes as a potential drug targets. One of them is hypoxanthine-guanine phosphoribosyltransferase (HGPRT, E.C. 18.104.22.168). The Center for Structural Genomics of Infectious Diseases has determined four X-ray structures of the HGPRT (hpt-1) enzyme from Bacillus anthracis str. 'Ames Ancestor'. In two apo-protein structures, sucrose (SUC) and 2-(N-morpholino)ethanesulfonic acid (MES) mimic the protein’s substrates. Two other structures have products, guanosine 5’-monophosphate (GMP) and inosine 5'-monophosphate (IMP), bound in the active site. Comparison of all four structures may provide new insights on substrate recognition, product release, possible feedback inhibition and drug development.
Last Updated March 01, 2011
Last Reviewed February 01, 2011