Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies showed that Staphylococcus aureus expresses a collagen-binding MSCRAMM (Microbial Surface Component Recognizing Adhesive Matrix Molecules), CNA, that is necessary and sufficient for S. aureus cells to adhere to cartilage and is a virulence factor in experimental septic arthritis. We have now used a monoclonal antibody (mAb) approach to further analyze the structure and function of CNA. 22 mAbs raised against the minimal ligand binding domain, CNA-(151-318), were shown to bind to the MSCRAMM with similar affinity. All mAbs appear to recognize conformation-dependent epitopes that were mapped throughout the CNA-(151-318) domain using a chimeric strategy where segments of CNA are grafted on ACE, a structurally related MSCRAMM from Enterococcus faecalis. These mAbs were able to inhibit (125)I-collagen binding to CNA-(151-318) as well as to intact S. aureus cells. They also interfered with the attachment of bacteria to collagen substrates. Furthermore, some of the mAbs could effectively displace (125)I-collagen bound to the bacteria. These displacing mAbs were also able to detach bacteria that had adhered to a collagen substrate in a preincubation, raising the possibility that some of the mAbs may be used as therapeutic agents.
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PMID:Monoclonal antibodies to CNA, a collagen-binding microbial surface component recognizing adhesive matrix molecules, detach Staphylococcus aureus from a collagen substrate. 1099 41

We have determined the crystal structure of the ligand binding segment of the Enterococcus faecalis collagen binding MSCRAMM ACE (microbial surface components recognizing adhesive matrix molecules adhesin of collagen from enterococci). This segment is composed of two subdomains, N(1) and N(2), each adopting an IgG-like fold and forming a putative collagen binding surface at the interface between the two subdomains. This structure is very similar to that recently reported for CNA, the collagen binding MSCRAMM of Staphylococcus aureus, for which a unique ligand binding mechanism called the Collagen Hug was proposed. We suggest that ACE binds collagen by a similar mechanism and present the first biochemical evidence for this binding model. Replacing residues in the putative collagen binding trench of ACE N(2) with Ala residues affected collagen binding. A closed conformation of ACE stabilized by an engineered disulfide bond is unable to bind collagen. Finally, the importance of the residues in the N(2) extension in stabilizing the MSCRAMM-ligand complex is demonstrated by selected point and truncation mutations.
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PMID:The Enterococcus faecalis MSCRAMM ACE binds its ligand by the Collagen Hug model. 1739 80

Arcanobacterium pyogenes, an opportunistic pathogen of economically important food animals, is the causative agent of liver abscesses in feedlot cattle, osteomyelitis in turkeys, and pneumonia and arthritis in pigs. Previous studies identified the first A. pyogenes adhesin, CbpA, a protein located on the bacterial surface which has the ability to bind collagen and promotes adhesion to the host cells. The protein has an N-terminal ligand-binding region (region A) and a C-terminal repetitive domain (region B). In this study we found that CbpA bound to almost all the collagen types tested but not to other proteins, and it displayed a propensity to interact with several collagenous peptides derived by CNBr cleavage of type I and II collagens. The K(D) values of CbpA for type I and II collagens and collagen peptides determined by solid-phase binding assay and intrinsic tryptophan fluorescence were in the range of 1-15 nM. It was also found that CbpA and its A region bound fibronectin, and that collagen and fibronectin interacted with distinct subsites. Anti-CbpA antibodies were effective at inhibiting both binding of isolated CbpA and bacterial adhesion to immobilized collagen, suggesting that CbpA is a functional collagen-binding adhesin. Analysis of the immunological cross-reactivity of CbpA with antibodies against other bacterial collagen-binding proteins indicated that CbpA is immunologically related to ACE from Enterococcus faecalis but not to CNA from Staphylococcus aureus or Acm from Enterococcus faecium. Far-UV and near-UV circular dichroism spectra showed that full-length CbpA and its region A are mainly composed of beta-sheet with only a minor alpha-helical component and that both the proteins have a well-defined tertiary structure.
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PMID:Functional and structural properties of CbpA, a collagen-binding protein from Arcanobacterium pyogenes. 1790 37