Document 0824
 DOCN  M9550824
 TI    The structure of unliganded reverse transcriptase from the human
       immunodeficiency virus type 1.
 DT    9505
 AU    Rodgers DW; Gamblin SJ; Harris BA; Ray S; Culp JS; Hellmig B; Woolf DJ;
       Debouck C; Harrison SC; Department of Molecular and Cellular Biology,
       Harvard University,; Cambridge, MA 02138.
 SO    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6. Unique Identifier :
       AIDSLINE MED/95166801
 AB    The crystal structure of the reverse transcriptase (RT) from the type 1
       human immunodeficiency virus has been determined at 3.2-A resolution.
       Comparison with complexes between RT and the polymerase inhibitor
       Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. &
       Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an
       oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D.,
       Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark,
       P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci.
       USA 90, 6320-6324] reveals changes associated with ligand binding. The
       enzyme is a heterodimer (p66/p51), with domains labeled fingers, thumb,
       palm, and connection in both subunits, and a ribonuclease H domain in
       the larger subunit only. The most striking difference between RT and
       both complex structures is the change in orientation of the p66 thumb
       (approximately 33 degrees rotation). Smaller shifts relative to the core
       of the molecule were also found in other domains, including the p66
       fingers and palm, which contain the polymerase active site. Within the
       polymerase catalytic region itself, there are no rearrangements between
       RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66
       palm near the polymerase active site, a region that is well-packed
       hydrophobic core in the unliganded enzyme. Room for the drug is provided
       by movement of a small beta-sheet within the palm domain of the
       Nevirapine complex. The rearrangement within the palm and thumb, as well
       as domain shifts relative to the enzyme core, may prevent correct
       placement of the oligonucleotide substrate when the drug is bound.
 DE    Binding Sites  Crystallography, X-Ray  DNA-Binding Proteins/CHEMISTRY
       HIV-1/*ENZYMOLOGY  Protein Conformation  Pyridines/CHEMISTRY  Reverse
       Transcriptase/ANTAGONISTS & INHIB/*CHEMISTRY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).