Linked Life Data

14579358

Source:http://linkedlifedata.com/resource/pubmed/id/14579358

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-10-27
pubmed:databankReference
pubmed:abstractText
It is well established that the fully formed polymerase active site of the DNA repair enzyme, polymerase beta (pol beta), including two bound Mg2+ cations and the nucleoside triphosphate (dNTP) substrate, exists at only one point in the catalytic cycle just prior to the chemical nucleotidyl transfer step. The structure of the active conformation has been the subject of much interest as it relates to the mechanism of the chemical step and also to the question of fidelity assurance. Although crystal structures of ternary pol beta-(primer-template) DNA-dNTP complexes have provided the main structural features of the active site, they are necessarily incomplete due to intentional alterations (e.g., removal of the 3'OH groups from primer and substrate) needed to obtain a structure from midcycle. Working from the crystal structure closest to the fully formed active site [Protein Data Bank (PDB) code: 1bpy], two molecular dynamics (MD) simulations of the solvated ternary complex were performed: one with the missing 3'OHs restored, via modeling, to the primer and substrate, and the other without restoration of the 3'OHs. The results of the simulations, together with ab initio optimizations on simplified active-site models, indicate that the missing primer 3'OH in the crystal structure is responsible for a significant perturbation in the coordination sphere of the catalytic cation and allow us to suggest several corrections and additions to the active-site structure as observed by crystallography. In addition, the calculations help to resolve questions raised regarding the protonation states of coordinating ligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1097-0134
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
667-82
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Characterization of the active site of DNA polymerase beta by molecular dynamics and quantum chemical calculation.
pubmed:affiliation
Computational Biosciences Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.