4mql | pdb_00004mql

Crystal structure of Antigen 85C-C209S mutant

spinqualitylabelsall models 4mql, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mql is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BTB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A85C_MYCTU The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM. Publication Abstract from PubMed The increasing prevalence of drug-resistant tuberculosis highlights the need for identifying new antitubercular drugs that can treat these infections. The antigen 85 (Ag85) complex has emerged as an intriguing mycobacterial drug target due to its central role in synthesizing major components of the inner and outer leaflets of the mycobacterial outer membrane. Here we identify ebselen (EBS) as a potent inhibitor of the Mycobacterium tuberculosis Ag85 complex. Mass spectrometry data show that EBS binds covalently to a cysteine residue (C209) located near the Ag85C active site. The crystal structure of Ag85C in the presence of EBS shows that C209 modification restructures the active site, thereby disrupting the hydrogen-bonded network within the active site that is essential for enzymatic activity. C209 mutations display marked decreases in enzymatic activity. These data suggest that compounds using this mechanism of action will strongly inhibit the Ag85 complex and minimize the selection of drug resistance. Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen.,Favrot L, Grzegorzewicz AE, Lajiness DH, Marvin RK, Boucau J, Isailovic D, Jackson M, Ronning DR Nat Commun. 2013;4:2748. doi: 10.1038/ncomms3748. PMID:24193546 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antigen 85 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA