Structural Basis of Murein Peptide Specificity of a g-D-Glutamyl-L-Diamino Acid Endopeptidase

• Published in: Structure (London) Vol. 17; no. 2; pp. 303 - 313
• Main Authors: Xu, Qingping, Sudek, Sebastian, McMullan, Daniel, Miller, Mitchell D, Geierstanger, Bernhard, Jones, David H, Krishna, S Sri, Spraggon, Glen, Bursalay, Badry, Abdubek, Polat, Acosta, Claire, Ambing, Eileen, Astakhova, Tamara, Axelrod, Herbert L, Carlton, Dennis, Caruthers, Jonathan, Chiu, Hsiu-Ju, Clayton, Thomas, Deller, Marc C
• Format: Journal Article
• Language: English
• Published: 01.02.2009
• Subjects: Anabaena variabilis; Cyanobacteria; Nostoc punctiforme
• ISSN: 0969-2126
• DOI: 10.1016/j.str.2008.12.008

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 g-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.