Structure of the streptococcal cell wall C5a peptidase.
Open accessAbstract
The structure of a cell surface enzyme from a gram-positive pathogen has been determined to 2-A resolution. Gram-positive pathogens have a thick cell wall to which proteins and carbohydrate are covalently attached. Streptococcal C5a peptidase (SCP), is a highly specific protease and adhesin/invasin. Structural analysis of a 949-residue fragment of the [D130A,S512A] mutant of SCP from group B Streptococcus (S. agalactiae, SCPB) revealed SCPB is composed of five distinct domains. The N-terminal subtilisin-like protease domain has a 134-residue protease-associated domain inserted into a loop between two beta-strands. This domain also contains one of two Arg-Gly-Asp (RGD) sequences found in SCPB. At the C terminus are three fibronectin type III (Fn) domains. The second RGD sequence is located between Fn1 and Fn2. Our analysis suggests that SCP binding to integrins by the RGD motifs may stabilize conformational changes required for substrate binding.
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The structure determined by Brown et al. (2005) was obtained with a recombinant mutant protein expressed in E. coli with the asp and ser of catalytic triad replaced by alanines and without pro-peptide; this structure has the histidine of catalytic triad separated by 20 Å from active position.
“The structure determined by Brown et al. (2005) was obtained with a recombinant mutant protein expressed in Escherichia coli with the asp and ser of the catalytic triad replaced by alanines and without the pro-peptide. This structure has the histidine of the catalytic triad separated by 20 Å from the active position (Brown et al., 2005).”
From Modeled Structure of the Cell Envelope Proteinase of Lactococcus lactis (2020) · cites this paper as Brown et al., 2005
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- Authors
- Brown, C. K., Gu, Z.-Y., Matsuka, Y. V., Purushothaman, S. S., Winter, L. A., Cleary, P. P., Olmsted, S. B., Ohlendorf, D. H., & Earhart, C. A.
- Affiliations
- University of Minnesota (US)
- ORCID
- Brown, C. Kent
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-12-12
- Volume
- 102
- Issue
- 51
- Pages
- 18391-18396
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1317908
- OpenAlex
- W2135032011
- Semantic Scholar
- e0eebf4a87e90b31d1371fadcc27abe2764177da
- Cited by
- 70
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Minnesota
- National Institutes of Health
- National Institute on Aging (R01AG050607)
- National Institute of Allergy and Infectious Diseases (R01AI020016, R01 AI50607, R01AI057585)
- Brookhaven National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- protein structure, RGD motif, integrin binding, fibronectin type III domain, adhesins, conformational change, substrate binding, Gram-positive bacterial cell wall
- MeSH terms
- Amino Acid Sequence, Cell Wall, Models, Molecular, Endopeptidases, Protein Binding, Streptococcus agalactiae, Protein Structure, Tertiary, Crystallography, X-Ray, Adhesins, Bacterial, Amino Acid Motifs, Protein Structure, Quaternary
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