Energy analysis of chemistry for correct insertion by DNA polymerase beta.
X-ray crystallographic structures of human DNA polymerase beta with nonhydrolyzable analogs containing all atoms in the active site required for catalysis provide a secure starting point for a theoretical analysis (quantum mechanics/molecular mechanics) of the mechanism of chemistry without biasing of modeling assumptions as required in previous studies. These structures provide the basis for a detailed quantum mechanics/molecular mechanics study of the path for the complete transfer of a monophosphate nucleoside donor to the sugar acceptor in the active site. The reaction is largely associative with the main energetic step preceded by proton transfer from the terminal primer deoxyribose O3' to Asp-256. The key residues that provide electrostatic stabilization of the transition state are identified and compared with those identified by mutational studies.
Lin
Ping
P
Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Pedersen
Lars C
LC
Batra
Vinod K
VK
Beard
William A
WA
Wilson
Samuel H
SH
Pedersen
Lee G
LG
D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011522:Protons; D011789:Quantum Theory; D055672:Static Electricity; D013816:Thermodynamics
D009711:Nucleotides; D011522:Protons; D019951:DNA Polymerase beta