5e5l

Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom

spinqualitylabelsall models 5e5l, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5e5l 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 1.89Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LDT1_MYCTU Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is thought to play a role in adaptation to the nonreplicative state of M.tuberculosis. Publication Abstract from PubMed Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the beta-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of beta-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for beta-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria. We have characterized the molecular mechanisms responsible for inhibition of L,D-transpeptidases of Mycobacterium tuberculosis and a range of bacteria including ESKAPE pathogens, and used this information to design, synthesize and test simplified carbapenems with potent antibacterial activity. Non-classical transpeptidases yield insight into new antibacterials.,Kumar P, Kaushik A, Lloyd EP, Li SG, Mattoo R, Ammerman NC, Bell DT, Perryman AL, Zandi TA, Ekins S, Ginell SL, Townsend CA, Freundlich JS, Lamichhane G Nat Chem Biol. 2016 Nov 7. doi: 10.1038/nchembio.2237. PMID:27820797 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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