5O29
Lytic transglycosylase in action
Summary for 5O29
| Entry DOI | 10.2210/pdb5o29/pdb |
| Descriptor | Transglycosylase (2 entities in total) |
| Functional Keywords | lytic transglycosylases, acid/base catalysis, peptidoglycan, bacteria, hydrolase |
| Biological source | Neisseria meningitidis |
| Total number of polymer chains | 1 |
| Total formula weight | 65684.61 |
| Authors | Williams, A.H.,Hoauz, A.,Boneca, I.G. (deposition date: 2017-05-19, release date: 2018-03-14, Last modification date: 2024-11-13) |
| Primary citation | Williams, A.H.,Wheeler, R.,Rateau, L.,Malosse, C.,Chamot-Rooke, J.,Haouz, A.,Taha, M.K.,Boneca, I.G. A step-by-stepin crystalloguide to bond cleavage and 1,6-anhydro-sugar product synthesis by a peptidoglycan-degrading lytic transglycosylase. J. Biol. Chem., 293:6000-6010, 2018 Cited by PubMed Abstract: Lytic transglycosylases (LTs) are a class of enzymes important for the recycling and metabolism of peptidoglycan (PG). LTs cleave the β-1,4-glycosidic bond between -acetylmuramic acid (MurNAc) and GlcNAc in the PG glycan strand, resulting in the concomitant formation of 1,6-anhydro--acetylmuramic acid and GlcNAc. No LTs reported to date have utilized chitins as substrates, despite the fact that chitins are GlcNAc polymers linked via β-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 utilizes chitopentaose ((GlcNAc)) 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 identified trapped intermediates, unpredicted substrate rearrangements, sugar distortions, and a conserved crystallographic water molecule bound to the catalytic 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 understanding of the mechanisms of LTs in bacterial cell wall biology. PubMed: 29483188DOI: 10.1074/jbc.RA117.001095 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3785 Å) |
Structure validation
Download full validation report
