Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1998 Aug 3;17(15):4535-42.
doi: 10.1093/emboj/17.15.4535.

The Structure of HIV-1 Reverse Transcriptase Complexed With an RNA Pseudoknot Inhibitor

Affiliations
Free PMC article

The Structure of HIV-1 Reverse Transcriptase Complexed With an RNA Pseudoknot Inhibitor

J Jaeger et al. EMBO J. .
Free PMC article

Abstract

Small RNA pseudoknots, selected to bind human immunodeficiency virus type 1 (HIV-1) reverse transcriptase tightly, are potent inhibitors of reverse transcriptase. The co-crystal structure of reverse transcriptase complexed with a 33 nucleotide RNA pseudoknot has been determined by fitting the ligand into a high quality, 4-fold averaged 4.8 A resolution electron density map. The RNA is kinked between stems S1 and S2, thereby optimizing its contacts with subunits of the heterodimer. Its binding site extends along the cleft that lies between the polymerase and RNase H active sites, partially overlaps with that observed for duplex DNA and presumably overlaps some portion of the tRNA site. Stem S2 and loop L1 stabilize the 'closed' conformation of the polymerase through extensive electrostatic interactions with several basic residues in helix I of the p66 thumb and in the p66 fingers domain. Presumably, this RNA ligand inhibits reverse transcriptase by binding to a site that partly overlaps the primer-template binding site.

Similar articles

See all similar articles

Cited by 38 articles

See all "Cited by" articles

References

    1. J Mol Biol. 1968 Apr 28;33(2):491-7 - PubMed
    1. J Biol Chem. 1994 May 6;269(18):13080-3 - PubMed
    1. Nucleic Acids Res. 1985 Mar 11;13(5):1717-31 - PubMed
    1. Nucleic Acids Res. 1987 Nov 11;15(21):8783-98 - PubMed
    1. Biochemistry. 1989 Apr 4;28(7):2985-91 - PubMed

Publication types

MeSH terms

Associated data

LinkOut - more resources

Feedback