4M6G
Structure of the Mycobacterium tuberculosis peptidoglycan amidase Rv3717 in complex with L-Alanine-iso-D-Glutamine reaction product
Summary for 4M6G
Entry DOI | 10.2210/pdb4m6g/pdb |
Related | 4M6H 4M6I |
Descriptor | Peptidoglycan Amidase Rv3717, ZINC ION, ALANINE, ... (5 entities in total) |
Functional Keywords | structural genomics, niaid, national institute of allergy and infectious diseases, tb structural genomics consortium, tbsgc, zn binding, hydrolase |
Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Cellular location | Periplasm : I6Y4D2 |
Total number of polymer chains | 1 |
Total formula weight | 23798.25 |
Authors | Prigozhin, D.M.,Mavrici, D.,Huizar, J.P.,Vansell, H.J.,Alber, T.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2013-08-09, release date: 2013-09-18, Last modification date: 2024-10-16) |
Primary citation | Prigozhin, D.M.,Mavrici, D.,Huizar, J.P.,Vansell, H.J.,Alber, T. Structural and Biochemical Analyses of Mycobacterium tuberculosis N-Acetylmuramyl-L-alanine Amidase Rv3717 Point to a Role in Peptidoglycan Fragment Recycling. J.Biol.Chem., 288:31549-31555, 2013 Cited by PubMed Abstract: Peptidoglycan hydrolases are key enzymes in bacterial cell wall homeostasis. Understanding the substrate specificity and biochemical activity of peptidoglycan hydrolases in Mycobacterium tuberculosis is of special interest as it can aid in the development of new cell wall targeting therapeutics. In this study, we report biochemical and structural characterization of the mycobacterial N-acetylmuramyl-L-alanine amidase, Rv3717. The crystal structure of Rv3717 in complex with a dipeptide product shows that, compared with previously characterized peptidoglycan amidases, the enzyme contains an extra disulfide-bonded β-hairpin adjacent to the active site. The structure of two intermediates in assembly reveal that Zn(2+) binding rearranges active site residues, and disulfide formation promotes folding of the β-hairpin. Although Zn(2+) is required for hydrolysis of muramyl dipeptide, disulfide oxidation is not required for activity on this substrate. The orientation of the product in the active site suggests a role for a conserved glutamate (Glu-200) in catalysis; mutation of this residue abolishes activity. The product binds at the head of a closed tunnel, and the enzyme showed no activity on polymerized peptidoglycan. These results point to a potential role for Rv3717 in peptidoglycan fragment recycling. PubMed: 24019530DOI: 10.1074/jbc.M113.510792 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.104 Å) |
Structure validation
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