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A point mutation at the subunit interface of hypoxanthine–guanine–xanthine phosphoribosyltransferase impairs activity: role of oligomerization in catalysis
Author(s) -
Subbayya I.N.Sujay,
Balaram Hemalatha
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02826-0
Subject(s) - phosphoribosyltransferase , hypoxanthine , hypoxanthine guanine phosphoribosyltransferase , chemistry , xanthine , mutant , guanine , biochemistry , tetramer , allosteric regulation , purine , enzyme , point mutation , stereochemistry , nucleotide , gene
Hypoxanthine–guanine–xanthine phosphoribosyltransferase (HGXPRT) from Plasmodium falciparum catalyzes the phosphoribosylation of hypoxanthine, guanine and xanthine. The functionally active form of HGXPRT is a tetramer but interface residues do not contribute to catalysis. Here we report the characterization of an interface mutant Y96C, which has a decreased k cat , an increase in the K m for phosphoribosyl pyrophosphate (PRPP) and no change in K m for the purine bases when compared to the wild type enzyme. The mutant enzyme does not tetramerize in the presence of PRPP, unlike the wild type in which the tetramer is stabilized by PRPP. This is the first report of a HGXPRT mutation, at a unique interface where non‐adjacent subunits interact, that impairs catalysis.