2yhh

Microvirin:mannobiose complex

spinqualitylabelsall models 2yhh, 2 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yhh is a 1 chain structure with sequence from Microcystis aeruginosa. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MAN Related: 2y1s Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Lectins that bind surface envelope glycoprotein gp120 of HIV with high avidity can potently inhibit viral entry. Yet properties such as multivalency that facilitate strong interactions can also cause nonspecific binding and toxicity. The cyanobacterial lectin microvirin (MVN) is unusual as it potently inhibits HIV-1 with negligible toxicity compared with cyanovirin-N (CVN), its well studied antiviral homolog. To understand the structural and mechanistic basis for these differences, we solved the solution structure of MVN free and in complex with its ligand Manalpha(1-2)Man, and we compared specificity and time windows of inhibition with CVN and Manalpha(1-2)Man-specific mAb 2G12. We show by NMR and analytical ultracentrifugation that MVN is monomeric in solution, and we demonstrate by NMR that Manalpha(1-2)Man-terminating carbohydrates interact with a single carbohydrate-binding site. Synchronized infectivity assays show that 2G12, MVN, and CVN inhibit entry with distinct kinetics. Despite shared specificity for Manalpha(1-2)Man termini, combinations of the inhibitors are synergistic suggesting they recognize discrete glycans and/or dynamic glycan conformations on gp120. Entry assays employing amphotropic viruses show that MVN is inactive, whereas CVN potently inhibits both. In addition to demonstrating that HIV-1 can be inhibited through monovalent interactions, given the similarity of the carbohydrate-binding site common to MVN and CVN, these data suggest that gp120 behaves as a clustered glycan epitope and that multivalent-protein interactions achievable with CVN but not MVN are required for inhibition of some viruses. Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity.,Shahzad-ul-Hussan S, Gustchina E, Ghirlando R, Clore GM, Bewley CA J Biol Chem. 2011 Jun 10;286(23):20788-96. Epub 2011 Apr 6. PMID:21471192 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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