Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site.
Lysine was substituted for a conserved arginine at position 199 of the schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a > or = 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate (PRPP). The possible functional role of R199 in tertiary structure, as well as in the binding of PRPP, is interpreted in the context of the reported three dimensional structure for the human HPRT.
Craig
S P
SP
Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan. scraig@unc.edu
Focia
P J
PJ
Fletterick
R J
RJ
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D012547:Schistosoma
D010754:Phosphoribosyl Pyrophosphate; D001120:Arginine; D007041:Hypoxanthine Phosphoribosyltransferase; D008239:Lysine