If the plug-in named ChemScape Chime is properly installed on your computer, you should see a rotating 3D HIV-Tat molecule. The molecule can be moved by clicking it with the left button of your mouse and its characteristics, including automatic rotation, can be modified by clicking it with the right button.
To download the plug-in: 
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Heparin binds extracellular HIV-1 Tat protein and modulates its HIV-long terminal repeat (LTR)-transactivating activity (M., Rusnati, D., Coltrini, P., Oreste, G., Zoppetti, A., Albini, D., Noonan, F. d’Adda di Fagagna, M. Giacca, and M. Presta (1997) J. Biol. Chem. 272, 11313-11320).
On this basis, the glutathione-S-transferase (GST)- TatR49/52/53/55/56/57A mutant, in which six arginine residues within the basic domain of Tat were mutagenized to alanine residues, was compared to GST-Tat for its capacity to bind immobilized heparin. Dissociation of the GST-TatR49/52/53/55/56/57A/heparin complex occurred at ionic strength significantly lower than that required to dissociate the GST-Tat/heparin complex. Accordingly, heparin binds immobilized GST-Tat and GST-TatR49/52/53/55/56/57A with a dissociation constant equal to 0.3 mM and 1.0 mM, respectively. Also, the synthetic basic domain Tat(41-60) competes with GST-Tat for heparin binding.
Suramin inhibits 3H-heparin/Tat interaction, 125I-GST-Tat internalization and the LTR-transactivating activity of extracellular Tat in HL3T1 cells, and prevents 125I-GST-Tat binding and cell proliferation in Tat-overexpressing T53 cells. The suramin derivative 14C-PNU 145156E binds immobilized GST-Tat with a dissociation constant 5 times higher than heparin and is unable to bind GST-TatR49/52/53/55/56/57A. Even though heparin was an antagonist more potent than suramin, modifications of the backbone structure in selected suramin derivatives originated Tat antagonists whose potency was close to that shown by heparin.
In conclusion, suramin derivatives bind the basic
domain of Tat, prevent Tat/heparin and Tat/cell surface interactions, and
inhibit the biological activity of extracellular Tat. Our data demonstrate
that tailored polysulfonated compounds represent potent extracellular Tat
inhibitors of possible therapeutical value.
J. Biol.
Chem. (1998) 273: 16027-16037
