O4-Alkylated-2-Deoxyuridine Repair byO6-Alkylguanine DNA Alkyltransferase is Augmented by a C5-Fluorine Modification

ChemBioChem ◽  
2018 ◽  
Vol 19 (6) ◽  
pp. 575-582 ◽  
Author(s):  
Lauralicia Sacre ◽  
Derek K. O'Flaherty ◽  
Philippe Archambault ◽  
William Copp ◽  
Gilles H. Peslherbe ◽  
...  
Keyword(s):  
Dna Alkyltransferase ◽  
Fluorine Modification

Structural insights into the repair mechanism of AGT for methyl-induced DNA damage

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Rajendra P. Koirala ◽  
Rudramani Pokhrel ◽  
Prabin Baral ◽  
Purushottam B. Tiwari ◽  
Prem P. Chapagain ◽  
...  
Keyword(s):  
Covalent Bond ◽  
Cancer Therapeutics ◽  
Md Simulations ◽  
Structural Features ◽  
Umbrella Sampling ◽  
Repair Mechanism ◽  
Structural Investigations ◽  
Methylated Dna ◽  
Dna Base ◽  
Dna Alkyltransferase

Abstract Methylation induced DNA base-pairing damage is one of the major causes of cancer. O6-alkylguanine-DNA alkyltransferase (AGT) is considered a demethylation agent of the methylated DNA. Structural investigations with thermodynamic properties of the AGT-DNA complex are still lacking. In this report, we modeled two catalytic states of AGT-DNA interactions and an AGT-DNA covalent complex and explored structural features using molecular dynamics (MD) simulations. We utilized the umbrella sampling method to investigate the changes in the free energy of the interactions in two different AGT-DNA catalytic states, one with methylated GUA in DNA and the other with methylated CYS145 in AGT. These non-covalent complexes represent the pre- and post-repair complexes. Therefore, our study encompasses the process of recognition, complex formation, and separation of the AGT and the damaged (methylated) DNA base. We believe that the use of parameters for the amino acid and nucleotide modifications and for the protein-DNA covalent bond will allow investigations of the DNA repair mechanism as well as the exploration of cancer therapeutics targeting the AGT-DNA complexes at various functional states as well as explorations via stabilization of the complex.

Interferon inducers increase O6-alkylguanine-DNA alkyltransferase in the rat liver

1990 ◽  
Vol 11 (1) ◽  
pp. 181-183 ◽  
Author(s):  
Riccardo Bertini ◽  
Paolo Coccia ◽  
Paolo Pagani ◽  
Cristina Marinello ◽  
Mario Salmona ◽  
...  
Keyword(s):  
Rat Liver ◽  
Interferon Inducers ◽  
Dna Alkyltransferase

scholarly journals Human O6 -alkylguanine-DNA alkyltransferase: protection against alkylating agents and sensitization to dibromoalkanes

1999 ◽  
Vol 20 (11) ◽  
pp. 2089-2094 ◽  
Author(s):  
Nieves Abril ◽  
Francisco L. Luque-Romero ◽  
Fred C. Christians ◽  
Lance P. Encell ◽  
Lawrence A. Loeb ◽  
...  
Keyword(s):  
Alkylating Agents ◽  
Dna Alkyltransferase

Isolation and cDNA cloning of a rat; O6-alkyllguanine-DNA-alkyltransferase gene, molecelar analysis of expression in rat liver

1991 ◽  
Vol 12 (4) ◽  
pp. 727-733 ◽  
Author(s):  
P.M. Potter ◽  
J.A. Rafferty ◽  
L. Cawkwell ◽  
M.C. Wilkinson ◽  
D.P. Cooper ◽  
...  
Keyword(s):  
Cdna Cloning ◽  
Rat Liver ◽  
Dna Alkyltransferase

Inactivation ofO6-Alkylguanine-DNA Alkyltransferase. 1. NovelO6-(Hetarylmethyl)guanines Having Basic Rings in the Side Chain

1998 ◽  
Vol 41 (26) ◽  
pp. 5265-5271 ◽  
Author(s):  
R. Stanley McElhinney ◽  
Dorothy J. Donnelly ◽  
Joan E. McCormick ◽  
Jane Kelly ◽  
Amanda J. Watson ◽  
...  
Keyword(s):  
Side Chain ◽  
Dna Alkyltransferase
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