Substitution of an alanine residue for glycine 146 in TMP kinase from Escherichia coli is responsible for bacterial hypersensitivity to bromodeoxyuridine.
The wild-type TMP kinases from Escherichia coli and from a strain hypersensitive to 5-bromo-2'-deoxyuridine were characterized comparatively. The mutation at codon 146 causes the substitution of an alanine residue for glycine in the enzyme, which is accompanied by changes in the relative affinities for 5-Br-UMP and TMP compared to those of the wild-type TMP kinase. Plasmids carrying the wild-type tmk gene from Escherichia coli or Bacillus subtilis, but not the defective tmk gene, restored the resistance to bromodeoxyuridine of an E. coli mutant strain.
Laboratoire de Chimie Structurale des Macromolécules, Institut Pasteur, 75724 Paris Cedex 15, France.
L
L
Tourneux
N
N
Bucurenci
I
I
Lascu
H
H
Sakamoto
G
G
Briand
A M
AM
Gilles
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000963:Antimetabolites / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002384:Catalysis; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D005998:Glycine / Q000378:metabolism; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D017386:Sequence Homology, Amino Acid; D014169:Transformation, Bacterial
D000963:Antimetabolites; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D001973:Bromodeoxyuridine; D000409:Alanine; D005998:Glycine