Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by chloramphenicol phosphotransferase activity

Izard, T

T. Izard, Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by chloramphenicol phosphotransferase activity, PROTEIN SCI, 10(8), 2001, pp. 1508-1513

19

INGLESE

Article

Biochemistry & Biophysics

PROTEIN SCIENCE

0961-8368 → ACNP

10

8

2001

1508 - 1513

ISI

0961-8368(200108)10:8<1508:SBFCTI>2.0.ZU;2-X

Streptomyces venezuelae synthesizes chloramphenicol (Cm), an inhibitor of r ibosomal pegtidyl transferase activity, thereby inhibiting bacterial growth . The producer escapes autoinhibition by its own secondary metabolite throu gh phosphorylation of Cm by chloramphenicol phosphotransferase (CPT). In ad dition to active site binding, CPT binds its product 9-phosphoryl-Cm, in an alternate product binding site. To address the mechanisms of Cm tolerance of the producer, the crystal structures of CPT were determined in complex w ith either the nonchlorinated Cm (2-N-Ac-Cm) at 3.1 Angstrom resolution or the antibiotic's immediate precursor, the p-amino analog p-NH2-Cm, at 2.9 A ngstrom resolution. Surprisingly, p-NH2-Cm binds CPT in a novel fashion. Ad ditionally, neither 2-N-Ac-Cm nor p-NH2-Cm binds to the secondary product b inding site.