Characterization of new mutations in pyrazinamide-resistant strains of Mycobacterium tuberculosis and identification of conserved regions important for the catalytic activity of the pyrazinamidase PncA.
A new set of mutations, including transposition of the insertion sequence IS6110, was identified in the pncA gene from 19 pyrazinamide-resistant Mycobacterium tuberculosis strains. Alignment of the PncA protein from M. tuberculosis with homologous proteins from different bacterial species revealed three highly conserved regions in PncA which may play an important role in the processing of pyrazinamide.
Lemaitre
N
N
Laboratoire de Recherche Moléculaire sur les Antibiotiques, Faculté de Médecine Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France.
Sougakoff
W
W
Truffot-Pernot
C
C
Jarlier
V
V
D000581:Amidohydrolases / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D011718:Pyrazinamide / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D011718:Pyrazinamide; D000581:Amidohydrolases; C022490:pyrazinamide deamidase