6fpn

Lytic transglycosylase in action

spinqualitylabelsall models 6fpn, resolution 1.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fpn is a 1 chain structure with sequence from Neimb. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 5o2n, 5024, 501j, 5029 Gene: NMB1949 (NEIMB) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Lytic transglycosylases (LTs) are a class of enzymes important for the recycling and metabo-lism of peptidoglycan (PG). LTs cleave the beta-1,4-glycosidic bond between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) in the PG glycan strand, resulting in the concomitant formation of 1,6-anhydro-MurNAc and GlcNAc. No LTs reported to date have utilized chitins as sub-strates, despite the fact that chitins are GlcNAc pol-ymers linked via beta-1,4-glycosidic bonds, which are the known site of chemical activity for LTs. Here, we demonstrate enzymatically that LtgA, a non-canonical, substrate-permissive LT from Neisseria meningitidis, utilizes chitopentaose ((GlcNAc)5) as a substrate to produce three newly identified sugars: 1,6-anhydro-chitobiose, 1,6-anhydro-chitotriose and 1,6-anhydro-chitotetraose. Although LTs have been widely studied, their complex reactions have not previously been visualized in the crystalline state because macromolecular PG is insoluble. Here, we visualized the cleavage of the glycosidic bond and the liberation of GlcNAc-derived residues by LtgA, followed by the synthesis of atypical 1,6-anhydro-GlcNAc derivatives. In addition to the newly identified anhydro-chitin products, we identi-fied trapped intermediates, unpredicted substrate rearrangements, sugar distortions, and a conserved crystallographic water molecule bound to the cata-lytic glutamate of a high-resolution native LT. This study enabled us to propose a revised alternative mechanism for LtgA that could also be applicable to other LTs. Our work contributes to the understand-ing of the mechanisms of LTs in bacterial cell wall biology. A step-by-step in crystallo guide to bond cleavage and 1,6-anhydro sugar product synthesis by a peptidoglycan degrading lytic transglycosylase.,Williams AH, Wheeler R, Rateau L, Malosse C, Chamot-Rooke J, Haouz A, Taha MK, Boneca IG J Biol Chem. 2018 Feb 26. pii: RA117.001095. doi: 10.1074/jbc.RA117.001095. PMID:29483188 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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