Crystal structure of Bacillus anthracis transpeptidase enzyme CapD.
Bacillus anthracis elaborates a poly-{gamma}-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. The enzyme CapD generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of B. anthracis. The capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. Here, we present the crystal structures of the {gamma}-glutamyltranspeptidase CapD with and without {alpha}-l-Glu-l-Glu dipeptide, a non-hydrolyzable analog of poly-{gamma}-d-glutamic acid, in the active site. Purified CapD displays transpeptidation activity in vitro, and its structure reveals an active site broadly accessible for poly-{gamma}-glutamate binding and processing. Using structural and biochemical information, we derive a mechanistic model for CapD catalysis whereby Pro{sup 427}, Gly{sup 428}, and Gly{sup 429} activate the catalytic residue of the enzyme, Thr{sup 352}, and stabilize an oxyanion hole via main chain amide hydrogen bonds.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE Office of Science (SC)
- DOE Contract Number:
- DE-AC02-06CH11357
- OSTI ID:
- 964639
- Report Number(s):
- ANL/BIO/JA-64579; JBCHA3; TRN: US200919%%513
- Journal Information:
- J. Biol. Chem., Vol. 284, Issue 36 ; Sep. 4, 2009; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- ENGLISH
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