3A07

Crystal Structure of Actinohivin; Potent anti-HIV Protein

Summary for 3A07

• Entry DOI: 10.2210/pdb3a07/pdb
• Descriptor: Actinohivin, SODIUM ION (3 entities in total)
• Functional Keywords: carbohydrate-binding module family 13, antiviral protein, lectin
• Biological source: actinomycete (Longispora albida)
• Total number of polymer chains: 2
• Total formula weight: 26069.84

Authors

Tsunoda, M.,Suzuki, K.,Sagara, T.,Takenaka, A. (deposition date: 2009-03-04, release date: 2009-08-25, Last modification date: 2024-11-13)

Primary citation

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.
Mechanism by which the lectin actinohivin blocks HIV infection of target cells
Proc.Natl.Acad.Sci.USA, 106:15633-15638, 2009

PubMed Abstract: 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.

PubMed: 19717426
DOI: 10.1073/pnas.0907572106

Experimental method

X-RAY DIFFRACTION (1.19 Å)