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Titolo:
Identification, substrate specificity, and inhibition of the Streptococcuspneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH)
Autore:
Khandekar, SS; Gentry, DR; Van Aller, GS; Warren, P; Xiang, H; Silverman, C; Doyle, ML; Chambers, PA; Konstantinidis, AK; Brandt, M; Daines, RA; Lonsdale, JT;
Indirizzi:
Glaxo SmithKline, Dept Prot Biochem, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Prot Biochem, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Biol Struct, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Bioinformat, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Mechanist Enzymol, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Med Chem, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA Glaxo SmithKline, Dept Microbial Biochem, King Of Prussia, PA 19406 USA Glaxo SmithKline King Of Prussia PA USA 19406 ng Of Prussia, PA 19406 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 32, volume: 276, anno: 2001,
pagine: 30024 - 30030
SICI:
0021-9258(20010810)276:32<30024:ISSAIO>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
FATTY-ACID BIOSYNTHESIS; ESCHERICHIA-COLI K-12; MYCOBACTERIUM-TUBERCULOSIS; CRYSTAL-STRUCTURE; ANTIBIOTIC THIOLACTOMYCIN; ACTIVE-SITE; TARGET; EXPRESSION; CLONING; GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Khandekar, SS Glaxo SmithKline, Dept Prot Biochem, 709 Swedeland Rd, King Of Prussia, PA19406 USA Glaxo SmithKline 709 Swedeland Rd King Of Prussia PA USA 19406
Citazione:
S.S. Khandekar et al., "Identification, substrate specificity, and inhibition of the Streptococcuspneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH)", J BIOL CHEM, 276(32), 2001, pp. 30024-30030

Abstract

In the bacterial type II fatty acid synthase system, beta -ketoacyl-acyl carrier protein (ACP) synthase IH (FabH) catalyzes the condensation of acetyl-CoA with malonyl-ACP. We have identified, expressed, and characterized the Streptococcus pneumoniae homologue of Escherichia coli FabH. S. pneumoniae FabH is similar to 41, 39, and 38% identical in amino acid sequence to Bacillus subtilis, E. coli and Hemophilus influenzae FabH, respectively. The His-Asn-Cys catalytic triad present in other FabH molecules is conserved inS. pneumoniae FabH. The apparent K-m values for acetyl-CoA and malonyl-ACPwere determined to be 40.3 and 18.6 muM, respectively. Purified S. pneumoniae FabH preferentially utilized straight short-chain CoA primers. Similar to E. coli FabH, S. pneumoniae FabH was weakly inhibited by thiolactomycin. In contrast, inhibition of S. pneumoniae FabH by the newly developed compound SB418011 was very potent, with an IC50 value of 0.016 muM. SB418011 also inhibited E. coli and H. influenzae FabH with IC50 values of 1.2 and. 0.59 muM, respectively. The availability of purified and characterized S. pneumoniae FabH will greatly aid in structural studies of this class of essential bacterial enzymes and. facilitate the identification of small molecule inhibitors of type II fatty acid synthase with the potential to be novel andpotent antibacterial agents active against pathogenic bacteria.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 02:14:12