Document Detail


Effects of non-catalytic, distal amino acid residues on activity of E. coli DinB (DNA polymerase IV).
MedLine Citation:
PMID:  23034734     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
DinB is one of two Y family polymerases in E. coli and is involved in copying damaged DNA. DinB is specialized to bypass deoxyguanosine adducts that occur at the N(2) position, with its cognate lesion being the furfuryl adduct. Active site residues have been identified that make contact with the substrate and carry out deoxynucleotide triphosphate (dNTP) addition to the growing DNA strand. In DNA polymerases, these include negatively charged aspartate and glutamate residues (D8, D103, and E104 in E. coli DNA polymerase IV DinB). These residues position the essential magnesium ions correctly to facilitate nucleophilic attack by the primer hydroxyl group on the α-phosphate group of the incoming dNTP. To study the contribution of DinB residues to lesion bypass, the computational methods THEMATICS and POOL were employed. These methods correctly predict the known active site residues, as well as other residues known to be important for activity. In addition, these methods predict other residues involved in substrate binding as well as more remote residues. DinB variants with mutations at the predicted positions were constructed and assayed for bypass of the N(2) -furfuryl-dG lesion. We find a wide range of effects of predicted residues, including some mutations that abolish damage bypass. Moreover, most of the DinB variants constructed are unable to carry out the extension step of lesion bypass. The use of computational prediction methods represents another tool that will lead to a more complete understanding of translesion DNA synthesis. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
Authors:
Jason M Walsh; Ramya Parasuram; Pradyumna R Rajput; Eriks Rozners; Mary Jo Ondrechen; Penny J Beuning
Related Documents :
9699714 - Dna immunization targeting the skin: molecular control of adaptive immunity.
24312634 - Tal effector specificity for base 0 of the dna target is altered in a complex, effecto...
8668934 - Direct dna immunization of mice with plasmid dna encoding the tegument protein pp65 (pp...
12885344 - Safety of interleukin-12 gene therapy against cancer: a murine biodistribution and toxi...
9765284 - A vaccinia virus late transcription factor with biochemical and molecular identity to a...
17406564 - Contour-clamped homogeneous electric field electrophoresis of staphylococcus aureus.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  -     ISSN:  1098-2280     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Exploring copper(i)-based dye-sensitized solar cells: a complementary experimental and TD-DFT invest...
Next Document:  Comparison of specialist and nonspecialist care pathways for adolescents with anorexia nervosa and r...