Crystal structure of adenine phosphoribosyltransferase from Leishmania tarentolae: potential implications for APRT catalytic mechanism

Biochim Biophys Acta. 2004 Jan 14;1696(1):31-9. doi: 10.1016/j.bbapap.2003.09.003.

Abstract

The three-dimensional structure of Leishmania tarentolae adenine phosphoribosyltransferase (APRT) in complex with adenosine-5-monophosphate (AMP) and a phosphate ion has been solved. Refinement against X-ray diffraction data extending to 2.2-A resolution led to a final crystallographic R factor of 18.3%. Structural comparisons amongst this APRT enzyme and other 'type I' PRTases whose structures have been determined reveal several important features of the PRTases catalytic mechanism. Based on structural superpositions and molecular interaction potential calculations, it was possible to suggest that the PRPP is the first substrate to bind, while the AMP is the last product to leave the active site, in accordance to recent kinetic studies performed with the Leishmania donovani APRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Phosphoribosyltransferase / biosynthesis
  • Adenine Phosphoribosyltransferase / chemistry*
  • Adenine Phosphoribosyltransferase / isolation & purification
  • Adenosine Monophosphate / chemistry
  • Animals
  • Binding Sites
  • Cations, Divalent
  • Leishmania / enzymology*
  • Magnesium / chemistry
  • Models, Molecular
  • Phosphoribosyl Pyrophosphate / chemistry
  • X-Ray Diffraction

Substances

  • Cations, Divalent
  • Adenosine Monophosphate
  • Phosphoribosyl Pyrophosphate
  • Adenine Phosphoribosyltransferase
  • Magnesium