Specificity and efficiency in activity of anti-HIV actinohivin for sugar binding

Abstract

Introduction HIV/AIDS is a major health concern, a global pandemic which remains a relatively uncontrolled infectious disease. Over 20 kinds of inhibitors targeting the HIV enzymes (e.g. reverse transcriptase, integrase and protease) are currently used as medicines to disturb the HIV lifecycle after HIV entry into cells. These antiretroviral drugs have recently been evaluated further for their dual effects as treatments and in preventing HIV infections. In addition, some proteins which are able to bind the surface glycoprotein of HIV are now expected to prevent HIV entry into cells. This effect on entry inhibition is also applicable to help suppress the spread of infection. Structurally, trimeric gp120 protruded from the HIV surface binds to human CD cell to initiate entry. Each gp120 is highly glycosylated to cover the surface with highmannose type glycans (HMTG). As candidates for suppressing gp120binding to susceptible cells, several carbohydrate-binding proteins (lectins) have been isolated and characterized. We succeeded in discovering a new lectin, actinohivin (hereafter designated AH) from an actinomycete, Longispora albida. This lectin possesses a potent, specific anti-HIV activity to inhibits the entry of various HIV-1 and HIV-2 strains into susceptible cells, as well as T-celltropic and macrophage-tropic syncytium formation. Therefore, we have at first determined the crystal structure of the apo form[1] and then that in complex with Man-α(1,2)-Man (hereafter MB) of HMTG by X-ray analyses.