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10.1038/ncomms12581 http://scihub22266oqcxt.onion/10.1038/ncomms12581 C5025758!5025758!27581223     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2016 ; 7 (ä): ä Nephropedia Template TP {{tp|p=27581223|t=2016. Identification of KasA as the cellular target of an anti-tubercular scaffold |pdf=|usr=}}{{27581223}} gab.com Text Identification of KasA as the cellular target of an anti-tubercular scaffold JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=27581223 #FOAvip Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis ?-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related ?-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis. Twit Text FOAVip Identification of KasA as the cellular target of an anti-tubercular scaffold ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=27581223 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27581223 #FOAvip English Wikipedia <ref>{{Cite pmid|27581223}}</ref> Identification of KasA as the cellular target of an anti-tubercular scaffold #MMPMID27581223 Abrahams KA; Chung Cw; Ghidelli-Disse S; Rullas J; Rebollo-López MJ; Gurcha SS; Cox JAG; Mendoza A; Jiménez-Navarro E; Martínez-Martínez MS; Neu M; Shillings A; Homes P; Argyrou A; Casanueva R; Loman NJ; Moynihan PJ; Lelièvre J; Selenski C; Axtman M; Kremer L; Bantscheff M; Angulo-Barturen I; Izquierdo MC; Cammack NC; Drewes G; Ballell L; Barros D; Besra GS; Bates RH Nat Commun 2016[]; 7 (ä): ä PMID27581223show ga Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis ?-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related ?-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis. äIdentification of KasA as the cellular target of an anti-tubercular sc(epmc).pdf DeepDyve Pubget Overpricing