scholarly journals Measuring rapid hydrogen exchange in the homodimeric 36 kDa HIV-1 integrase catalytic core domain

2011 ◽  
Vol 20 (9) ◽  
pp. 1643-1643
Author(s):  
Nicholas C. Fitzkee ◽  
Dennis A. Torchia ◽  
Ad Bax
Keyword(s):  
Hydrogen Exchange ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Hiv 1

scholarly journals Measuring rapid hydrogen exchange in the homodimeric 36 kDa HIV-1 integrase catalytic core domain

2011 ◽  
Vol 20 (3) ◽  
pp. 500-512 ◽  
Author(s):  
Nicholas C. Fitzkee ◽  
Dennis A. Torchia ◽  
Ad Bax
Keyword(s):  
Hydrogen Exchange ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Hiv 1

scholarly journals Effects of Mutations in Residues near the Active Site of Human Immunodeficiency Virus Type 1 Integrase on Specific Enzyme-Substrate Interactions

1998 ◽  
Vol 72 (6) ◽  
pp. 5046-5055 ◽  
Author(s):  
Jennifer L. Gerton ◽  
Sharron Ohgi ◽  
Mari Olsen ◽  
Joseph DeRisi ◽  
Patrick O. Brown
Keyword(s):  
Human Immunodeficiency Virus ◽  
Active Site ◽  
Catalytic Core Domain ◽  
Viral Dna ◽  
Catalytic Core ◽  
Core Domain ◽  
Immunodeficiency Virus ◽  
Close Proximity ◽  
Hiv 1

ABSTRACT The phylogenetically conserved catalytic core domain of human immunodeficiency virus type 1 (HIV-1) integrase contains elements necessary for specific recognition of viral and target DNA features. In order to identify specific amino acids that determine substrate specificity, we mutagenized phylogenetically conserved residues that were located in close proximity to the active-site residues in the crystal structure of the isolated catalytic core domain of HIV-1 integrase. Residues composing the phylogenetically conserved DD(35)E active-site motif were also mutagenized. Purified mutant proteins were evaluated for their ability to recognize the phylogenetically conserved CA/TG base pairs near the viral DNA ends and the unpaired dinucleotide at the 5′ end of the viral DNA, using disintegration substrates. Our findings suggest that specificity for the conserved A/T base pair depends on the active-site residue E152. The phenotype of IN(Q148L) suggested that Q148 may be involved in interactions with the 5′ dinucleotide of the viral DNA end. The activities of some of the proteins with mutations in residues in close proximity to the active-site aspartic and glutamic acids were salt sensitive, suggesting that these mutations disrupted interactions with DNA.

scholarly journals Non-Cryogenic Structure and Dynamics of HIV-1 Integrase Catalytic Core Domain by X-ray Free-Electron Lasers

2019 ◽  
Vol 20 (8) ◽  
pp. 1943 ◽  
Author(s):  
Jae-Hyun Park ◽  
Ji-Hye Yun ◽  
Yingchen Shi ◽  
Jeongmin Han ◽  
Xuanxuan Li ◽  
...  
Keyword(s):  
Free Electron ◽  
Genetic Material ◽  
Catalytic Triad ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
X Ray ◽  
Hiv 1 ◽  
Dynamic Profile ◽  
Good Agreement

HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140–153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

scholarly journals A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain

2016 ◽  
Vol 291 (45) ◽  
pp. 23569-23577 ◽  
Author(s):  
Disha Patel ◽  
Janet Antwi ◽  
Pratibha C. Koneru ◽  
Erik Serrao ◽  
Stefano Forli ◽  
...  
Keyword(s):  
Catalytic Core Domain ◽  
Integrase Inhibitors ◽  
Catalytic Core ◽  
Core Domain ◽  
Fragment Screening ◽  
New Class ◽  
Hiv 1

scholarly journals Genetic Analyses of DNA-Binding Mutants in the Catalytic Core Domain of Human Immunodeficiency Virus Type 1 Integrase

2005 ◽  
Vol 79 (4) ◽  
pp. 2493-2505 ◽  
Author(s):  
Richard Lu ◽  
Ana Limón ◽  
Hina Z. Ghory ◽  
Alan Engelman
Keyword(s):  
Dna Binding ◽  
Active Site ◽  
Class I ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Target Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The catalytic core domain (CCD) of human immunodeficiency virus type 1 (HIV-1) integrase (IN) harbors the enzyme active site and binds viral and chromosomal DNA during integration. Thirty-five CCD mutant viruses were constructed, paying particular attention to conserved residues in the Phe139-Gln146 flexible loop and abutting Ser147-Val165 amphipathic alpha helix that were implicated from previous in vitro work as important for DNA binding. Defective viruses were typed as class I mutants (specifically blocked at integration) or pleiotropic class II mutants (additional particle assembly and/or reverse transcription defects). Whereas HIV-1P145A and HIV-1Q146K grew like the wild type, HIV-1N144K and HIV-1Q148L were class I mutants, reinforcing previous results that Gln-148 is important for DNA binding and uncovering for the first time an important role for Asn-144 in integration. HIV-1Q62K, HIV-1H67E, HIV-1N120K, and HIV-1N155K were also class I mutants, supporting findings that Gln-62 and Asn-120 interact with viral and target DNA, respectively, and suggesting similar integration-specific roles for His-67 and Asn-155. Although results from complementation analyses established that IN functions as a multimer, the interplay between active-site and CCD DNA binding functions was unknown. By using Vpr-IN complementation, we determined that the CCD protomer that catalyzes integration also preferentially binds to viral and target DNA. We additionally characterized E138K as an intramolecular suppressor of Gln-62 mutant virus and IN. The results of these analyses highlight conserved CCD residues that are important for HIV-1 replication and integration and define the relationship between DNA binding and catalysis that occurs during integration in vivo.

scholarly journals The crystal structure of the catalytic core domain of HIV-1 integrase in a new crystal form

1996 ◽  
Vol 52 (a1) ◽  
pp. C155-C155
Author(s):  
F. Dyda ◽  
A. B. Hickman ◽  
T. M. Jenkins ◽  
A. Engelman ◽  
R. Craigie ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Crystal Form ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Hiv 1
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