title: Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase.
abstract: The crystal structures of two homologous endopeptidases from cyanobacteria Anabaena variabilis and Nostoc punctiforme were determined at 1.05 and 1.60 A resolution, respectively, and contain a bacterial SH3-like domain (SH3b) and a ubiquitous cell-wall-associated NlpC/P60 (or CHAP) cysteine peptidase domain. The NlpC/P60 domain is a primitive, papain-like peptidase in the CA clan of cysteine peptidases with a Cys126/His176/His188 catalytic triad and a conserved catalytic core. We deduced from structure and sequence analysis, and then experimentally, that these two proteins act as gamma-D-glutamyl-L-diamino acid endopeptidases (EC 3.4.22.-). The active site is located near the interface between the SH3b and NlpC/P60 domains, where the SH3b domain may help define substrate specificity, instead of functioning as a targeting domain, so that only muropeptides with an N-terminal L-alanine can bind to the active site.
authors.affiliation: Joint Center for Structural Genomics, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA.
authors.forename: Qingping
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authors.lastname: Nigoghossian
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authors.lastname: Oommachen
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authors.lastname: Zubieta
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authors.lastname: Hodgson
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authors.lastname: Wooley
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authors.lastname: Deacon
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mesh_terms: D000595:Amino Acid Sequence; D046870:Anabaena variabilis / Q000737:chemistry / Q000201:enzymology; D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046937:Nostoc / Q000737:chemistry / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D018909:src Homology Domains
chemical_list: D010446:Peptide Fragments; D010457:Peptidoglycan; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C038279:gamma-D-glutamyl-L-diaminoacid endopeptidase