2jmv
Solution structure of scytovirin refined against residual dipolar couplings
Structural highlights
FunctionSVN_SCYVA Has strong anti-HIV activity against T-tropic strains of HIV-1 and weaker activity against M-tropic strains of HIV-1. Inhibits HIV-1 fusion and infection of CD4 LTR beta-gal cells in vitro. Inhibits fusion of HIV infected CEM-SS cells with uninfected CEM-SS cells, and fusion of HIV-1 Env expressing HL2/3 cells with CD4 LTR beta-gal cells. Binds to HIV gp120, HIV gp160 and to a lesser extent HIV gp41. Binding to HIV gp120 is glycosylation dependent. Binds with high specificity to the tetrasaccharide Man-alpha-1,2-Man-alpha-1,6-Man-alpha-1,6-Man and also binds the higher-order oligosaccharides oligomannose 8 and oligomannose 9. Does not bind to monosaccharides, complex or hybrid N-linked oligosaccharides or chitin.[1] [2] [3] [4] Publication Abstract from PubMedThe solution structure of the potent 95 residue anti-HIV protein scytovirin has been determined and two carbohydrate-binding sites have been identified. This unique protein, containing five structurally important disulfide bonds, demonstrates a novel fold with no elements of extended regular secondary structure. Scytovirin contains two 39 residue sequence repeats, differing in only three amino acid residues, and each repeat has primary sequence similarity to chitin binding proteins. Both sequence repeats form similarly structured domains, with the exception of one region. The result is two carbohydrate-binding sites with substantially different affinities. The unusual fold clusters aromatic residues in both sites, suggesting a binding mechanism similar to other known hevein-like carbohydrate-binding proteins but differing in carbohydrate specificity. Scytovirin, originally isolated from the cyanobacterium Scytonema varium, holds potential as an HIV entry inhibitor for both therapeutic and prophylactic anti-HIV applications. The high-resolution structural studies reported are an important initial step in unlocking the therapeutic potential of scytovirin. The novel fold of scytovirin reveals a new twist for antiviral entry inhibitors.,McFeeters RL, Xiong C, O'Keefe BR, Bokesch HR, McMahon JB, Ratner DM, Castelli R, Seeberger PH, Byrd RA J Mol Biol. 2007 Jun 1;369(2):451-61. Epub 2007 Mar 20. PMID:17434526[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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