Structural highlights
Function
[VCP_VACCW] Serves to protect the virus against complement attack by inhibiting both classical and alternative pathways of complement activation. Binds C3b and C4b.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might provide useful structural information for interpreting interactions of suramin with many proteins.
Structural basis for antagonism by suramin of heparin binding to vaccinia complement protein.,Ganesh VK, Muthuvel SK, Smith SA, Kotwal GJ, Murthy KH Biochemistry. 2005 Aug 16;44(32):10757-65. PMID:16086578[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Isaacs SN, Kotwal GJ, Moss B. Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):628-32. PMID:1731333
- ↑ Girgis NM, Dehaven BC, Fan X, Viner KM, Shamim M, Isaacs SN. Cell surface expression of the vaccinia virus complement control protein is mediated by interaction with the viral A56 protein and protects infected cells from complement attack. J Virol. 2008 May;82(9):4205-14. doi: 10.1128/JVI.02426-07. Epub 2008 Feb 20. PMID:18287241 doi:http://dx.doi.org/10.1128/JVI.02426-07
- ↑ Ganesh VK, Muthuvel SK, Smith SA, Kotwal GJ, Murthy KH. Structural basis for antagonism by suramin of heparin binding to vaccinia complement protein. Biochemistry. 2005 Aug 16;44(32):10757-65. PMID:16086578 doi:10.1021/bi050401x
