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Science 23 December 1994:
Vol. 266. no. 5193, pp. 1981 - 1986
DOI: 10.1126/science.7801124
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Articles

Science, Vol 266, Issue 5193, 1981-1986
Copyright © 1994 by American Association for the Advancement of Science

articles

Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases

F Dyda, AB Hickman, TM Jenkins, A Engelman, R Craigie, and DR Davies

Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0560.

HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 A resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with a extensive solvent-inaccessible interface of 1300 A2 per monomer.


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J. Biol. Chem. 275, 3421-3430
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Retroviral DNA Integration.
P. Hindmarsh and J. Leis (1999)
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H. Chen, S.-Q. Wei, and A. Engelman (1999)
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X. Wu, H. Liu, H. Xiao, J. A. Conway, E. Hehl, G. V. Kalpana, V. Prasad, and J. C. Kappes (1999)
J. Virol. 73, 2126-2135
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Structural Determinants of Metal-induced Conformational Changes in HIV-1 Integrase.
E. Asante-Appiah, S. H. Seeholzer, and A. M. Skalka (1998)
J. Biol. Chem. 273, 35078-35087
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Activation/Attenuation Model for RNase H. A ONE-METAL MECHANISM WITH SECOND-METAL INHIBITION.
J. L. Keck, E. R. Goedken, and S. Marqusee (1998)
J. Biol. Chem. 273, 34128-34133
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A Map of Interactions between the Proteins of a Retrotransposon.
S. J. S. Steele and H. L. Levin (1998)
J. Virol. 72, 9318-9322
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Specific and Independent Recognition of U3 and U5 att Sites by Human Immunodeficiency Virus Type 1 Integrase In Vivo.
T. Masuda, M. J. Kuroda, and S. Harada (1998)
J. Virol. 72, 8396-8402
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Resistance to the Anti-Human Immunodeficiency Virus Type 1 Compound L-Chicoric Acid Results from a Single Mutation at Amino Acid 140 of Integrase.
P. J. King and W. E. Robinson Jr. (1998)
J. Virol. 72, 8420-8424
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Three new structures of the core domain of HIV-1 integrase: An active site that binds magnesium.
Y. Goldgur, F. Dyda, A. B. Hickman, T. M. Jenkins, R. Craigie, and D. R. Davies (1998)
PNAS 95, 9150-9154
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Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: Implications for retroviral assembly mechanisms.
M. Yeager, E. M. Wilson-Kubalek, S. G. Weiner, P. O. Brown, and A. Rein (1998)
PNAS 95, 7299-7304
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Tn552 transposase catalyzes concerted strand transfer in vitro.
A. E. Leschziner, T. J. Griffin IV, and N. D. F. Grindley (1998)
PNAS 95, 7345-7350
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Structure-Based Mutational Analysis of the C-Terminal DNA-Binding Domain of Human Immunodeficiency Virus Type 1 Integrase: Critical Residues for Protein Oligomerization and DNA Binding.
R. A. P. Lutzke and R. H. A. Plasterk (1998)
J. Virol. 72, 4841-4848
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Effects of Mutations in Residues near the Active Site of Human Immunodeficiency Virus Type 1 Integrase on Specific Enzyme-Substrate Interactions.
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Identification of a nucleotide binding site in HIV-1 integrase.
R. R. Drake, N. Neamati, H. Hong, A. A. Pilon, P. Sunthankar, S. D. Hume, G. W. A. Milne, and Y. Pommier (1998)
PNAS 95, 4170-4175
   Abstract »    Full Text »    PDF »
Mapping Viral DNA Specificity to the Central Region of Integrase by Using Functional Human Immunodeficiency Virus Type 1/Visna Virus Chimeric Proteins.
M. Katzman and M. Sudol (1998)
J. Virol. 72, 1744-1753
   Abstract »    Full Text »    PDF »
Efficient Gap Repair Catalyzed In Vitro by an Intrinsic DNA Polymerase Activity of Human Immunodeficiency Virus Type 1 Integrase.
A. Acel, B. E. Udashkin, M. A. Wainberg, and E. A. Faust (1998)
J. Virol. 72, 2062-2071
   Abstract »    Full Text »    PDF »
The Application of a Homologous Recombination Assay Revealed Amino Acid Residues in an LTR-Retrotransposon That Were Critical for Integration.
A. Atwood, J. Choi, and H. L. Levin (1998)
J. Virol. 72, 1324-1333
   Abstract »    Full Text »    PDF »
Implication of a Central Cysteine Residue and the HHCC Domain of Moloney Murine Leukemia Virus Integrase Protein in Functional Multimerization.
G. A. Donzella, O. Leon, and M. J. Roth (1998)
J. Virol. 72, 1691-1698
   Abstract »    Full Text »    PDF »
Dicaffeoylquinic and Dicaffeoyltartaric Acids Are Selective Inhibitors of Human Immunodeficiency Virus Type 1 Integrase.
B. McDougall, P. J. King, B. W. Wu, Z. Hostomsky, M. G. Reinecke, and W. E. Robinson Jr. (1998)
Antimicrob. Agents Chemother. 42, 140-146
   Abstract »    Full Text »
Mode of Interaction of G-Quartets with the Integrase of Human Immunodeficiency Virus Type 1.
P. Cherepanov, J. A. Esté, R. F. Rando, J. O. Ojwang, G. Reekmans, R. Steinfeld, G. David, E. De Clercq, and Z. Debyser (1997)
Mol. Pharmacol. 52, 771-780
   Abstract »    Full Text »
The Core Domain of HIV-1 Integrase Recognizes Key Features of Its DNA Substrates.
J. L. Gerton and P. O. Brown (1997)
J. Biol. Chem. 272, 25809-25815
   Abstract »    Full Text »    PDF »
HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway.
P. Gallay, T. Hope, D. Chin, and D. Trono (1997)
PNAS 94, 9825-9830
   Abstract »    Full Text »    PDF »
Binding of Different Divalent Cations to the Active Site of Avian Sarcoma Virus Integrase and Their Effects on Enzymatic Activity.
G. Bujacz, J. Alexandratos, A. Wlodawer, G. Merkel, M. Andrake, R. A. Katz, and A. M. Skalka (1997)
J. Biol. Chem. 272, 18161-18168
   Abstract »    Full Text »    PDF »
A Metal-induced Conformational Change and Activation of HIV-1 Integrase.
E. Asante-Appiah and A. M. Skalka (1997)
J. Biol. Chem. 272, 16196-16205
   Abstract »    Full Text »    PDF »
Disruption of the terminal base pairs of retroviral DNA during integration..
B P Scottoline, S Chow, V Ellison, and P O Brown (1997)
Genes & Dev. 11, 371-382
   Abstract »    PDF »
Thermal Stability of Escherichia coli Ribonuclease HI and Its Active Site Mutants in the Presence and Absence of the Mg2+ Ion. PROPOSAL OF A NOVEL CATALYTIC ROLE FOR Glu48.
S. Kanaya, M. Oobatake, and Y. Liu (1996)
J. Biol. Chem. 271, 32729-32736
   Abstract »    Full Text »    PDF »


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