Crystal structure of adenine phosphoribosyltransferase from Leishmania tarentolae: potential implications for APRT catalytic mechanism.
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.
Silva
M
M
Laboratory of Protein Crystallography and Structural Biology, Physics Institute of São Carlos, University of São Paulo-USP, Av. Trabalhador Sãocarlense 400, PO Box 369, 13566-590, São Carlos, SP, Brazil.
Silva
C H T P
CH
Iulek
J
J
Oliva
G
G
Thiemann
O H
OH
D000228:Adenine Phosphoribosyltransferase / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D000249:Adenosine Monophosphate / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent; D007891:Leishmania / Q000201:enzymology*; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D010754:Phosphoribosyl Pyrophosphate / Q000737:chemistry; D014961:X-Ray Diffraction
D002413:Cations, Divalent; D000249:Adenosine Monophosphate; D010754:Phosphoribosyl Pyrophosphate; D000228:Adenine Phosphoribosyltransferase; D008274:Magnesium