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GNF ID 100606: Crystal structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases

Xu, Qingping and Abdubeck, Polat and Chen, Connie and Chiu, Michelle and Feuerhelm, Julie and Grant, Joanna and Klock, Heath and Knuth, Mark and Okach, Linda and Nigoghossian, Edward and Puckett, Christina and Wooten, Tiffany and Lesley, Scott and Stolz, Barbara (2010) GNF ID 100606: Crystal structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases. Acta Crystallographica Section F: Structural Biology and Crystallization Communications, F66. pp. 1-11. ISSN 1744-3091

Abstract

Crystal structure of a highly specific γ-D-glutamyl-L-diamino acid endopeptidases YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu reveals structural basis for substrate specificity of NlpC/P60 family cysteine peptidases.
Dipeptidyl-peptidase VI of Bacillus sphaericus and YkfC of Bacillus subtilis were both characterized previously as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC orthologue from Bacillus cereus (BcYkfC) at 1.8 Å resolution reveals that it contains two N-terminal, bacterial SH3 domains (SH3b) in addition to a C-terminal catalytic NlpC/P60 domain, which is ubiquitous in the very large family of cell-wall related, cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enables the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu, hence provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both interact with the free amine group of the alanine. This structural feature allows us to define a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components, an NlpC/P60 domain attached to an SH3b domain, for assembly of a YkfC-like active site.

Item Type: Article
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Additional Information: grant requirement B. Stolz is NOT an author -- NVS contact person for GNF manuscript approval. This manuscript shall NOT be copied to the OAK internet.
Keywords: γ-D-glutamyl-L-diamino acid endopeptidase, cell-wall recycling, NlpC/P60, SH3b, cysteine peptidase, enzyme specificity
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/3113

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