6iyw

Crystal sturucture of L,D-transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with Imipenem adduct

spinqualitylabelsall models 6iyw, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6iyw is a 6 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 1.6Å Ligands: GOL, IM2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LDT2_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. Publication Abstract from PubMed L,D-transpeptidases, widely distributed in bacteria and even in the difficult-to-treat ESKAPE pathogens, can confer antibacterial resistance against the traditional beta-lactam antibiotics through bypass of the 4-->3 transpeptide linkage. LdtMt2, a l,d-transpeptidase in Mycobacteria tuberculosis, is essential for bacterial virulence and is considered as a potential anti-tuberculosis target inhibited by carbapenems. Diverse interaction modes between carbapenems and LdtMt2 have been reported, there are only limited evidences to validate those interaction modes. Herein, we identified the stable binding states of two carbapenems, imipenem and ertapenem, via crystallographic and biochemical studies, discovered that they adopt similar binding conformations. We further demonstrate the absence of the 1-beta-methyl group in imipenem and the presence of both Y308 and Y318 residues in LdtMt2 synergistically resulted in one order of magnitude higher affinity for imipenem than ertapenem. Our study provides a structural basis for the rational drug design and evolvement of novel carbapenems against bacterial L,D-transpeptidases. The 1-beta-methyl group confers a lower affinity of l,d-transpeptidase LdtMt2 for ertapenem than for imipenem.,Zhao F, Hou YJ, Zhang Y, Wang DC, Li DF Biochem Biophys Res Commun. 2019 Mar 5;510(2):254-260. doi:, 10.1016/j.bbrc.2019.01.082. Epub 2019 Jan 25. PMID:30686533 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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