2pys

Crystal Structure of a Five Site Mutated Cyanovirin-N with a Mannose Dimer Bound at 1.8 A Resolution

spinqualitylabelsall models 2pys, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pys is a 2 chain structure with sequence from Nostoc ellipsosporum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: MAN, PRD_900111 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CVN_NOSEL Mannose-binding lectin. 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 Cyanovirin-N (CV-N) is a 101 amino acid cyanobacterial lectin with potent antiviral activity against HIV, mediated by high-affinity binding to branched N-linked oligomannosides on the viral surface envelope protein gp120. The protein contains two carbohydrate-binding domains, A and B, each of which binds short oligomannosides independently in vitro. The interaction to gp120 could involve either a single domain or both domains simultaneously; it is not clear which mode would elicit the antiviral activity. The model is complicated by the formation of a domain-swapped dimer form, in which part of each domain is exchanged between two monomers, which contains four functional carbohydrate-binding domains. To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity, we engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a [P51G] mutation prevents the formation of domain-swapped dimers under physiological conditions. Here, we present the crystal structures at 1.8 A of the free and of the dimannose-bound forms of P51G-m4-CVN, revealing a monomeric structure in which only domain B is bound to dimannose. P51G-m4-CVN binds gp120 with an affinity almost 2 orders of magnitude lower than wt CV-N and is completely inactive against HIV. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions. Our findings show that the presence of at least two oligomannoside-binding sites, either by the presence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity. A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity.,Fromme R, Katiliene Z, Giomarelli B, Bogani F, Mc Mahon J, Mori T, Fromme P, Ghirlanda G Biochemistry. 2007 Aug 14;46(32):9199-207. Epub 2007 Jul 18. PMID:17636873 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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