scholarly journals Crystal Structure ofDeinococcus radioduransRecQ Helicase Catalytic Core Domain: The Interdomain Flexibility

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sheng-Chia Chen ◽  
Chi-Hung Huang ◽  
Chia Shin Yang ◽  
Tzong-Der Way ◽  
Ming-Chung Chang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Deinococcus Radiodurans ◽  
Domain Architecture ◽  
Genome Integrity ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Winged Helix ◽  
Dna Helicases ◽  
E Coli

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.

scholarly journals A Crystal Structure of the Catalytic Core Domain of an Avian Sarcoma and Leukemia Virus Integrase Suggests an Alternate Dimeric Assembly

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23032 ◽  
Author(s):  
Allison Ballandras ◽  
Karen Moreau ◽  
Xavier Robert ◽  
Marie-Pierre Confort ◽  
Romain Merceron ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Leukemia Virus ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Avian Sarcoma

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

scholarly journals Targeting neddylation E2s: a novel therapeutic strategy in cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yi-Chao Zheng ◽  
Yan-Jia Guo ◽  
Bo Wang ◽  
Chong Wang ◽  
M. A. A. Mamun ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Therapeutic Strategy ◽  
Neural Precursor Cell ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
E3 Ligases ◽  
Ubiquitin Conjugating Enzyme ◽  
E2 Enzymes ◽  
Conjugating Enzyme

AbstractUbiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.

scholarly journals Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA

2010 ◽  
Vol 1 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Xue Yao ◽  
Shasha Fang ◽  
Wentao Qiao ◽  
Yunqi Geng ◽  
Yuequan Shen
Keyword(s):  
Crystal Structures ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Target Dna

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.

Unexpected Isomerisation of a Fragment Analogue During Fragment-Based Screening of HIV Integrase Catalytic Core Domain

2015 ◽  
Vol 68 (12) ◽  
pp. 1871
Author(s):  
John H. Ryan ◽  
Karen E. Jarvis ◽  
Roger J. Mulder ◽  
Craig L. Francis ◽  
G. Paul Savage ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Binding Site ◽  
Hiv Integrase ◽  
Catalytic Core Domain ◽  
Aromatic Carboxylic Acid ◽  
Catalytic Core ◽  
Core Domain ◽  
Acid Fragment ◽  
Immunodeficiency Virus

Fragment-based screening of human immunodeficiency virus type 1 (HIV) integrase revealed several aromatic carboxylic acid fragment hits, some of which bound weakly at the site on the HIV-integrase catalytic core domain that binds the lens epithelium-derived growth factor (LEDGF). Virtual screening of an internal database identified an analogue that bound with higher affinity and in an isomerised form to the LEDGF binding site. The starting lactone was stable in CDCl3; however, an unexpected isomerisation process occurred in [D6]DMSO to give the same isomer found in the LEDGF binding site. This hit led directly to a series of low-micromolar LEDGF inhibitors and, via a scaffold hop, to a series of allosteric binding site inhibitors.

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