Article ; Online: Mechanistic cross-talk between DNA/RNA polymerase enzyme kinetics and nucleotide substrate availability in cells: Implications for polymerase inhibitor discovery.
The Journal of biological chemistry
2020 Volume 295, Issue 39, Page(s) 13432–13443
Abstract: ... parameters of cellular and viral DNA and RNA polymerases with respect to cellular levels of their nucleotide ... substrates. This broad perspective exposes a remarkable co-evolution scenario of DNA polymerase enzyme ... Enzyme kinetic analysis reveals a dynamic relationship between enzymes and their substrates ...
| Abstract | Enzyme kinetic analysis reveals a dynamic relationship between enzymes and their substrates. Overall enzyme activity can be controlled by both protein expression and various cellular regulatory systems. Interestingly, the availability and concentrations of intracellular substrates can constantly change, depending on conditions and cell types. Here, we review previously reported enzyme kinetic parameters of cellular and viral DNA and RNA polymerases with respect to cellular levels of their nucleotide substrates. This broad perspective exposes a remarkable co-evolution scenario of DNA polymerase enzyme kinetics with dNTP levels that can vastly change, depending on cell proliferation profiles. Similarly, RNA polymerases display much higher |
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| MeSH term(s) | Animals ; DNA-Directed DNA Polymerase/metabolism ; DNA-Directed RNA Polymerases/antagonists & inhibitors ; DNA-Directed RNA Polymerases/metabolism ; Drug Discovery ; Enzyme Inhibitors/pharmacology ; Humans ; Kinetics ; Nucleotides/metabolism ; Substrate Specificity | |||||
| Chemical Substances | Enzyme Inhibitors ; Nucleotides ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) | |||||
| Language | English | |||||
| Publishing date | 2020-07-31 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Review | |||||
| ZDB-ID | 2997-x | |||||
| ISSN | 1083-351X ; 0021-9258 | |||||
| ISSN (online) | 1083-351X | |||||
| ISSN | 0021-9258 | |||||
| DOI | 10.1074/jbc.REV120.013746 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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