1. HIV integrase We have been engaged in a structural analysis of the HIV integrase, and have previously reported the crystallization and structure determination of the catalytic core domain, residues 50-212. We have now crystallized this core domain in several different crystal forms. Analysis of these crystals reveals more details about some of the residues that were disordered in the original structure. Crystals prepared in the presence of Mg++, a known cofactor, now show clear evidence for the binding of this cation at the active site of the enzyme. We have also prepared a variety of other fragments of the integrase in an effort to crystallize the core domain coupled to either or both of the remaining domains. Some encouraging results have been obtained but diffraction quality crystals have not yet been produced. 2. The Barrier to Autointegration Factor (BAF) BAF is a host factor that prevents the autointegration of the viral DNA. The molecule has been crystallized and the structure determined at 1.9A resolution. In the crystal the protein exists as a dimer. Comparison with previous NMR studies of this protein shows that there is close homology between the structures of the subunit monomers together with a small difference in forming the dimer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK036109-11
Application #
6105326
Study Section
Special Emphasis Panel (LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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Chiu, Thang K; Kubelka, Jan; Herbst-Irmer, Regine et al. (2005) High-resolution x-ray crystal structures of the villin headpiece subdomain, an ultrafast folding protein. Proc Natl Acad Sci U S A 102:7517-22
Chiu, Thang K; Davies, David R (2004) Structure and function of HIV-1 integrase. Curr Top Med Chem 4:965-77
Umland, Timothy C; Wolff, Edith C; Park, Myung Hee et al. (2004) A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex. J Biol Chem 279:28697-705