3a07

Crystal Structure of Actinohivin; Potent anti-HIV ProteinCrystal Structure of Actinohivin; Potent anti-HIV Protein

Structural highlights 3a07 is a 2 chain structure with sequence from Actsk. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Various lectins have attracted attention as potential microbicides to prevent HIV transmission. Their capacity to bind glycoproteins has been suggested as a means to block HIV binding and entry into susceptible cells. The previously undescribed lectin actinohivin (AH), isolated by us from an actinomycete, exhibits potent in vitro anti-HIV activity by binding to high-mannose (Man) type glycans (HMTGs) of gp120, an envelope glycoprotein of HIV. AH contains 114 aa and consists of three segments, all of which need to show high affinity to gp120 for the anti-HIV characteristic. To generate the needed mechanistic understanding of AH binding to HIV in anticipation of seeking approval for human testing as a microbicide, we have used multiple molecular tools to characterize it. AH showed a weak affinity to Manalpha(1-2)Man, Manalpha(1-2)Manalpha(1-2)Man, of HMTG (Man8 or Man9) or RNase B (which has a single HMTG), but exhibited a strong and highly specific affinity (K(d) = 3.4 x 10(-8) M) to gp120 of HIV, which contains multiple Man8 and/or Man9 units. We have compared AH to an alternative lectin, cyanovirin-N, which did not display similar levels of discrimination between high- and low-density HMTGs. X-ray crystal analysis of AH revealed a 3D structure containing three sugar-binding pockets. Thus, the strong specific affinity of AH to gp120 is considered to be due to multivalent interaction of the three sugar-binding pockets with three HMTGs of gp120 via the "cluster effect" of lectin. Thus, AH is a good candidate for investigation as a safe microbicide to help prevent HIV transmission. Mechanism by which the lectin actinohivin blocks HIV infection of target cells.,Tanaka H, Chiba H, Inokoshi J, Kuno A, Sugai T, Takahashi A, Ito Y, Tsunoda M, Suzuki K, Takenaka A, Sekiguchi T, Umeyama H, Hirabayashi J, Omura S Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15633-8. Epub 2009 Aug 26. PMID:19717426 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 3a07, resolution 1.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image