Identification of a mutation that relieves gamma-glutamyl kinase from allosteric feedback inhibition by proline.
A 1.75-kb DNA fragment containing the entire Escherichia coli proB+ gene has been sequenced. The proB locus encodes the structural gene for gamma-glutamyl kinase (GK), the enzyme responsible for the first step in proline biosynthesis, and the primary regulatory point of the pathway. We have previously reported the nucleotide (nt) sequence of a mutant proB gene isolated from an E. coli strain resistant to the toxic analog of proline, 3,4-dehydro-DL-proline (DHP). This mutant gene encodes a GK which is refractory to allosteric feedback inhibition by proline (DHPR). Comparison of the proB+ and DHPR proB sequences revealed a single base difference, an A-T to C-G transversion localized at nt position 428 within the amino acid (aa) coding region of proB. This mutation predicts an aa change from glutamic acid in the wild-type (wt) enzyme to alanine in the DHPR enzyme.
D000494:Allosteric Regulation / Q000187:drug effects; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005796:Genes; D005798:Genes, Bacterial; D009154:Mutation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000235:genetics*; D017851:Phosphotransferases (Carboxyl Group Acceptor); D011392:Proline / Q000494:pharmacology*
D004269:DNA, Bacterial; D011392:Proline; D010770:Phosphotransferases; D017851:Phosphotransferases (Carboxyl Group Acceptor); C020650:glutamate 5-kinase