Work has been initiated on a number of structural problems related to proteins derived from the HIV virus. These include RNAse H domain of reverse transcriptase, nef, and proteins of the immune system, in particular interleukin-1-beta and interleukin-8. The RNaseH domain has been purified in large amounts and N-15 and C-13 labeled protein has been obtained. Current work is being focused on resonance assignment using 3D heteronuclear NMR methods. Complete assignments of interleukin-lo have been obtained, the secondary structure elucidated and a low resolution 3D structure determined. The high resolution 3D structure of the interleukin-8 dimer in solution has been determined. In addition we have determined the high resolution 3D structure of the zinc finger domain of a human enhancer binding protein which binds to the regulatory region in the long terminal repeat of the HIV genome.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Barrientos, Laura G; Gronenborn, Angela M (2005) The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy. Mini Rev Med Chem 5:21-31
Ding, Keyang; Gronenborn, Angela M (2004) Sensitivity-enhanced IPAP experiments for measuring one-bond 13C'-13Calpha and 13Calpha-1Halpha residual dipolar couplings in proteins. J Magn Reson 167:253-8
Barrientos, Laura G; Lasala, Fatima; Delgado, Rafael et al. (2004) Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity. Structure 12:1799-807
Ding, Keyang; Gronenborn, Angela M (2004) Protein Backbone 1H(N)-13Calpha and 15N-13Calpha residual dipolar and J couplings: new constraints for NMR structure determination. J Am Chem Soc 126:6232-3
Ishima, Rieko; Torchia, Dennis A; Lynch, Shannon M et al. (2003) Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J Biol Chem 278:43311-9
Louis, John M; Ishima, Rieko; Nesheiwat, Issa et al. (2003) Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties. J Biol Chem 278:6085-92
Katoh, Etsuko; Louis, John M; Yamazaki, Toshimasa et al. (2003) A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Protein Sci 12:1376-85
Barrientos, Laura G; Louis, John M; Ratner, Daniel M et al. (2003) Solution structure of a circular-permuted variant of the potent HIV-inactivating protein cyanovirin-N: structural basis for protein stability and oligosaccharide interaction. J Mol Biol 325:211-23
Ding, Keyang; Gronenborn, Angela M (2003) Sensitivity-enhanced 2D IPAP, TROSY-anti-TROSY, and E.COSY experiments: alternatives for measuring dipolar 15N-1HN couplings. J Magn Reson 163:208-14
Barrientos, Laura G; O'Keefe, Barry R; Bray, Mike et al. (2003) Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58:47-56

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