1. HIV integraseWe have been engaged in a structural analysis of the HIV integra previously reported the crystallization and structure determination of the catal residues 50-212. We have now crystallized this core domain in several different Analysis of these crystals reveals more details about some of the residues that the original structure. Crystals prepared in the presence of Mg++, a known cofa clear evidence for the binding of this cation at the active site of the enzyme. prepared a variety of other fragments of the integrase in an effort to crystalli coupled to either or both of the remaining domains. We have now been able to bi to the active site of the enzyme. This inhibitor binds centrally in the site and compound for antiviral drug design. Crystals have been examined with other inhib crystal form has been discovered.2. The Barrier to Autointegration Factor (BAF)B factor that prevents the autointegration of the viral DNA. The molecule has been the structure determined at 1.9A resolution. In the crystal the protein exists Comparison with previous NMR studies of this protein shows that there is close h between the structures of the subunit monomers together with a small but signifi between the two dimers. We also disagree with the NMR result in that we believe protein belongs, not to the helix turn helix motif but to the helix hairpin heli observed to bind nonspecifically to DNA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK036109-13
Application #
6432116
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2000
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Baxa, Ulrich; Cheng, Naiqian; Winkler, Dennis C et al. (2005) Filaments of the Ure2p prion protein have a cross-beta core structure. J Struct Biol 150:170-9
Davies, David (2005) A quiet life with proteins. Annu Rev Biophys Biomol Struct 34:1-20
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