PDBsum entry 3a07

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protein metals Protein-protein interface(s) links
Antiviral protein PDB id
Protein chains
116 a.a. *
_NA ×6
Waters ×317
* Residue conservation analysis
PDB id:
Name: Antiviral protein
Title: Crystal structure of actinohivin; potent anti-HIV protein
Structure: Actinohivin. Chain: a, b. Fragment: unp residues 43-160
Source: Actinomycete. Longispora albida. Organism_taxid: 237531. Strain: k97-0003
1.19Å     R-factor:   0.150     R-free:   0.163
Authors: M.Tsunoda,K.Suzuki,T.Sagara,A.Takenaka
Key ref:
H.Tanaka et al. (2009). Mechanism by which the lectin actinohivin blocks HIV infection of target cells. Proc Natl Acad Sci U S A, 106, 15633-15638. PubMed id: 19717426 DOI: 10.1073/pnas.0907572106
04-Mar-09     Release date:   25-Aug-09    
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Protein chains
Pfam   ArchSchema ?
Q9KWN0  (AHV_ACTSK) -  Actinohivin
160 a.a.
116 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1073/pnas.0907572106 Proc Natl Acad Sci U S A 106:15633-15638 (2009)
PubMed id: 19717426  
Mechanism by which the lectin actinohivin blocks HIV infection of target cells.
H.Tanaka, H.Chiba, J.Inokoshi, A.Kuno, T.Sugai, A.Takahashi, Y.Ito, M.Tsunoda, K.Suzuki, A.Takénaka, T.Sekiguchi, H.Umeyama, J.Hirabayashi, S.Omura.
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 Man alpha(1-2)Man, Man alpha(1-2)Man alpha(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.
  Selected figure(s)  
Figure 1.
Inhibition of AH binding to gp120 by α(1–2)Man oligomers. Open circle indicates Manα(1–2)Manα(1–2)Man, and solid square indicates Manα(1–2)Man.
Figure 5.
Effects of AH on gp120-gp120 antibody binding (A) and of gp120 antibody on AH–gp120 binding (B).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23151632 M.M.Hoque, K.Suzuki, M.Tsunoda, J.Jiang, F.Zhang, A.Takahashi, N.Ohbayashi, X.Zhang, H.Tanaka, S.Omura, and A.Takénaka (2012).
Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1-2)mannobiose moiety of gp120.
  Acta Crystallogr D Biol Crystallogr, 68, 1671-1679.
PDB code: 4den
  21314946 B.Hoorelbeke, E.J.Van Damme, P.Rougé, D.Schols, K.Van Laethem, E.Fouquaert, and J.Balzarini (2011).
Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity.
  Retrovirology, 8, 10.  
20585666 A.Ishiwata, Y.J.Lee, and Y.Ito (2010).
Recent advances in stereoselective glycosylation through intramolecular aglycon delivery.
  Org Biomol Chem, 8, 3596-3608.  
20842142 A.Takahashi, J.Inokoshi, M.Tsunoda, K.Suzuki, A.Takenaka, T.Sekiguchi, S.Omura, and H.Tanaka (2010).
Actinohivin: specific amino acid residues essential for anti-HIV activity.
  J Antibiot (Tokyo), 63, 661-665.  
20498311 B.Hoorelbeke, D.Huskens, G.Férir, K.O.François, A.Takahashi, K.Van Laethem, D.Schols, H.Tanaka, and J.Balzarini (2010).
Actinohivin, a broadly neutralizing prokaryotic lectin, inhibits HIV-1 infection by specifically targeting high-mannose-type glycans on the gp120 envelope.
  Antimicrob Agents Chemother, 54, 3287-3301.  
20559567 N.Matoba, A.S.Husk, B.W.Barnett, M.M.Pickel, C.J.Arntzen, D.C.Montefiori, A.Takahashi, K.Tanno, S.Omura, H.Cao, J.P.Mooney, C.V.Hanson, and H.Tanaka (2010).
HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity.
  PLoS One, 5, e11143.  
20162270 S.Xiong, J.Fan, and K.Kitazato (2010).
The antiviral protein cyanovirin-N: the current state of its production and applications.
  Appl Microbiol Biotechnol, 86, 805-812.  
20826337 T.Moulaei, S.R.Shenoy, B.Giomarelli, C.Thomas, J.B.McMahon, Z.Dauter, B.R.O'Keefe, and A.Wlodawer (2010).
Monomerization of viral entry inhibitor griffithsin elucidates the relationship between multivalent binding to carbohydrates and anti-HIV activity.
  Structure, 18, 1104-1115.
PDB codes: 3lky 3ll0 3ll1 3ll2
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