Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ATP GTP HYDROLYSIS IS REQUIRED FOR OXAZOLE AND THIAZOLE BIOSYNTHESIS IN THE PEPTIDE ANTIBIOTIC MICROCIN B17/
Autore:
MILNE JC; ELIOT AC; KELLEHER NL; WALSH CT;
Indirizzi:
HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL BOSTON MA 02115
Titolo Testata:
Biochemistry
fascicolo: 38, volume: 37, anno: 1998,
pagine: 13250 - 13261
SICI:
0006-2960(1998)37:38<13250:AGHIRF>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOUBLE-STRAND CLEAVAGE; DNA-GYRASE INHIBITOR; ESCHERICHIA-COLI; POSTTRANSLATIONAL MODIFICATIONS; BACKBONE MODIFICATIONS; CRYSTAL-STRUCTURE; BINDING; PROTEIN; MECHANISM; SYNTHASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Milne et al., "ATP GTP HYDROLYSIS IS REQUIRED FOR OXAZOLE AND THIAZOLE BIOSYNTHESIS IN THE PEPTIDE ANTIBIOTIC MICROCIN B17/", Biochemistry, 37(38), 1998, pp. 13250-13261

Abstract

In the maturation of the Escherichia coil antibiotic Microcin B17, the product of the mcbA gene is modified posttranslationally by the multimeric Microcin synthetase complex (composed of McbB, C, and D) to cyclize four Cys and four Ser residues to four thiazoles and four oxazoles, respectively. The purified synthetase shows an absolute requirementfor ATP or GTP in peptide substrate heterocyclization, with GTP one-third as effective as ATP in initial rate studies. The ATPase/GTPase activity of the synthetase complex is conditional in that ADP or GDP formation requires the presence of substrate; noncyclizable versions of McbA bind to synthetase, but do not induce the NTPase activity. The stoichiometry of ATP hydrolysis and heterocycle formation is 5:1 for a substrate that contains two potential sites of modification. However, athigh substrate concentrations (>50K(m)) heterocycle formation is inhibited, while ATPase activity occurs undiminished, consistent with uncoupling of NTP hydrolysis and heterocycle formation at high substrate concentrations. Sequence homology reveals that the McbD subunit has motifs reminiscent of the Walker B box in ATP utilizing enzymes and of motifs found in small G protein GTPases. Mutagenesis of three aspartatesto alanine in these motifs (D132, D147, and D199) reduced Microcin B17 production in vivo and heterocycle formation in vitro, suggesting that the 45 kDa McbD has a regulated ATPase/GTPase domain in its N-terminal region necessary for peptide heterocyclization.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/08/20 alle ore 20:57:42