5x80

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS MARR FAMILY PROTEIN RV2887 COMPLEX WITH SALICYLIC ACID

spinqualitylabelsall models 5x80, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x80 is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: SAL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HTMR_MYCTU Represses expression of the HQNO methyltransferase htm gene (Rv0560c) by binding to its promoter region (PubMed:26303802, PubMed:27432954, PubMed:28743871). Also represses the expression of at least five other genes, including the methyltransferase Rv0558 (PubMed:26303802). Binds salicylate (SA), para-aminosalicylic acid (PAS) and gemfibrozil (PubMed:28743871). Publication Abstract from PubMed MarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high affinity. Subsequent determination and analysis of Rv2887 crystal structures in apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion of helix alpha4 into the major groove. Ligand binding triggers rotation of the wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene Rv0560c. The structures provided here lay a foundation for the design of small molecules that target Rv2887, a potential new approach for the development of anti-mycobacterials. Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis.,Gao YR, Li DF, Fleming J, Zhou YF, Liu Y, Deng JY, Zhou L, Zhou J, Zhu GF, Zhang XE, Wang DC, Bi LJ Sci Rep. 2017 Jul 25;7(1):6471. doi: 10.1038/s41598-017-01705-4. PMID:28743871 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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