5ijw

Glutamate Racemase (MurI) from Mycobacterium smegmatis with bound D-glutamate, 1.8 Angstrom resolution, X-ray diffraction

spinqualitylabelsall models 5ijw, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ijw is a 2 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.76Å Ligands: DGL, IOD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MURI_MYCS2 Provides the (R)-glutamate required for cell wall biosynthesis. Publication Abstract from PubMed Glutamate racemase (MurI) is responsible for providing D-glutamate for peptidoglycan biosynthesis in bacteria and has been a favoured target in pharmaceutical drug design efforts. It has recently been proven to be essential in Mycobacterium tuberculosis, the causative organism of tuberculosis, a disease for which new medications are urgently needed. In the present study, we have determined the protein crystal structures of MurI from both M. tuberculosis and Mycobacterium smegmatis in complex with D-glutamate to 2.3 A and 1.8 A resolution respectively. These structures are conserved, but reveal differences in their active site architecture compared with that of other MurI structures. Furthermore, compounds designed to target other glutamate racemases have been screened but do not inhibit mycobacterial MurI, suggesting that a new drug design effort will be needed to develop inhibitors. A new type of MurI dimer arrangement has been observed in both structures, and this arrangement becomes the third biological dimer geometry for MurI found to date. The mycobacterial MurI dimer is tightly associated, with a KD in the nanomolar range. The enzyme binds D- and L-glutamate specifically, but is inactive in solution unless the dimer interface is mutated. We created triple mutants of this interface in the M. smegmatis glutamate racemase (D26R/R105A/G194R or E) that have appreciable activity (kcat=0.056-0.160 min(-1) and KM=0.26-0.51 mM) and can be utilized to screen proposed antimicrobial candidates for inhibition. Exploring the structure of glutamate racemase from Mycobacterium tuberculosis as a template for anti-mycobacterial drug discovery.,Poen S, Nakatani Y, Opel-Reading HK, Lasse M, Dobson RC, Krause KL Biochem J. 2016 May 1;473(9):1267-80. doi: 10.1042/BCJ20160186. Epub 2016 Mar 10. PMID:26964898 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutamate racemase 3D structures

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