Abstract

Current biochemical and structural data suggest that DNA polymerases from a variety of organisms use similar catalytic mechanisms for the synthesis of DNA. A more precise understanding of the reaction mechanisms of these proteins and the identification of structural features that dictate their substrate specificity, processivity, and other enzymatic properties await high resolution structures of DNA polymerases in catalytically-competent complexes with DNA and nucleotide substrates. The existing DNA polymerase structures are limited to enzymes that are adapted for distributive short-gap synthesis and, with one exception (Pol P), these structures are missing one or both substrates. We are investigating the structure of T7 DNA polymerase, its interaction with substrates, and its association with other proteins of the DNA replication fork complex.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
7P41RR012408-01A1
Application #
6283182
Study Section
Project Start
1998-09-30
Project End
1998-10-01
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Associated University-Brookhaven National Lab
Department
Type
DUNS #
City
Upton
State
NY
Country
United States
Zip Code
11973

  Publications

Sui, Xuewu; Farquhar, Erik R; Hill, Hannah E et al. (2018) Preparation and characterization of metal-substituted carotenoid cleavage oxygenases. J Biol Inorg Chem 23:887-901
Jacques, Benoit; Coinçon, Mathieu; Sygusch, Jurgen (2018) Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases. J Biol Chem 293:7737-7753
Fuller, Franklin D; Gul, Sheraz; Chatterjee, Ruchira et al. (2017) Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers. Nat Methods 14:443-449
Wangkanont, Kittikhun; Winton, Valerie J; Forest, Katrina T et al. (2017) Conformational Control of UDP-Galactopyranose Mutase Inhibition. Biochemistry 56:3983-3992
VanderLinden, Ryan T; Hemmis, Casey W; Yao, Tingting et al. (2017) Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. J Biol Chem 292:9493-9504
Song, Lingshuang; Yang, Lin; Meng, Jie et al. (2017) Thermodynamics of Hydrophobic Amino Acids in Solution: A Combined Experimental-Computational Study. J Phys Chem Lett 8:347-351
Orlova, Natalia; Gerding, Matthew; Ivashkiv, Olha et al. (2017) The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators. Nucleic Acids Res 45:3724-3737
Firestone, Ross S; Cameron, Scott A; Karp, Jerome M et al. (2017) Heat Capacity Changes for Transition-State Analogue Binding and Catalysis with Human 5'-Methylthioadenosine Phosphorylase. ACS Chem Biol 12:464-473
Roessler, Christian G; Agarwal, Rakhi; Allaire, Marc et al. (2016) Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography. Structure 24:631-640
Tajima, Nami; Karakas, Erkan; Grant, Timothy et al. (2016) Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature 534:63-8

Showing the most recent 10 out of 167 publications