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

RecQ DNA helicases are key enzymes in the maintenance of genome integrity, and they have functions in DNA replication, recombination, and repair. In contrast to most RecQs, RecQ fromDeinococcus radiodurans(DrRecQ) possesses an unusual domain architecture that is crucial for its remarkable ability to repair DNA. Here, we determined the crystal structures of the DrRecQ helicase catalytic core and its ADP-bound form, revealing interdomain flexibility in its first RecA-like and winged-helix (WH) domains. Additionally, the WH domain of DrRecQ is positioned in a different orientation from that of theE. coliRecQ (EcRecQ). These results suggest that the orientation of the protein during DNA-binding is significantly different when comparing DrRecQ and EcRecQ.

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Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results

Journal of the Turkish Chemical Society Section A Chemistry ◽

10.18596/jotcsa.287327 ◽

2016 ◽

Vol 4 (1) ◽

pp. 243-243

Author(s):

Selami Ercan

Keyword(s):

Molecular Dynamics ◽

Conformational Changes ◽

Catalytic Core Domain ◽

Catalytic Core ◽

Core Domain ◽

Molecular Dynamics Calculations ◽

Hiv 1

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The crystal structure of the catalytic core domain of endoglucanase I from Trichoderma reesei at 3.6 Å resolution, and a comparison with related enzymes 1 1Edited by K.Nagai

Journal of Molecular Biology ◽

10.1006/jmbi.1997.1243 ◽

1997 ◽

Vol 272 (3) ◽

pp. 383-397 ◽

Cited By ~ 167

Author(s):

Gerard J Kleywegt ◽

Jin-Yu Zou ◽

Christina Divne ◽

Gideon J Davies ◽

Irmgard Sinning ◽

...

Keyword(s):

Crystal Structure ◽

Trichoderma Reesei ◽

Catalytic Core Domain ◽

Catalytic Core ◽

Core Domain ◽

Endoglucanase I

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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

Journal of Virology ◽

10.1128/jvi.72.6.5046-5055.1998 ◽

1998 ◽

Vol 72 (6) ◽

pp. 5046-5055 ◽

Cited By ~ 57

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.

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

Protein Science ◽

10.1002/pro.582 ◽

2011 ◽

Vol 20 (3) ◽

pp. 500-512 ◽

Cited By ~ 23

Author(s):

Nicholas C. Fitzkee ◽

Dennis A. Torchia ◽

Ad Bax

Keyword(s):

Hydrogen Exchange ◽

Catalytic Core Domain ◽

Catalytic Core ◽

Core Domain ◽

Hiv 1

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Crystal structure of the catalytic core domain of the family 6 cellobiohydrolase II, Cel6A, from Humicola insolens, at 1.92 Å resolution

Biochemical Journal ◽

10.1042/0264-6021:3370297 ◽

1999 ◽

Vol 337 (2) ◽

pp. 297 ◽

Cited By ~ 30

Author(s):

Annabelle VARROT ◽

Sven HASTRUP ◽

Martin SCHÜLEIN ◽

Gideon J. DAVIES

Keyword(s):

Crystal Structure ◽

Catalytic Core Domain ◽

Catalytic Core ◽

Core Domain ◽

Humicola Insolens ◽

The Family ◽

Cellobiohydrolase Ii

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

International Journal of Molecular Sciences ◽

10.3390/ijms20081943 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1943 ◽

Cited By ~ 4

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.

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