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

Authors
Citation
T. Izard, Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by chloramphenicol phosphotransferase activity, PROTEIN SCI, 10(8), 2001, pp. 1508-1513
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
8
Year of publication
2001
Pages
1508 - 1513
Database
ISI
SICI code
0961-8368(200108)10:8<1508:SBFCTI>2.0.ZU;2-X
Abstract
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.