Atomistic simulations of competition between substrates binding to an enzyme
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| Vydáno v: | Biophysical Journal vol. 82, no. 5 (May 2002), p. 2326-2332 |
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Biophysical Society
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| On-line přístup: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 100 | 1 | |a Elcock, Adrian H | |
| 245 | 1 | |a Atomistic simulations of competition between substrates binding to an enzyme | |
| 260 | |b Biophysical Society |c May 2002 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Although the idea that electrostatic potentials generated by enzymes can guide substrates to active sites is well established, it is not always apppreciated that the same potentials can also promote the binding of molecules other than the intneded substrate, with the result that such enzymes might be snesitive to the presence of competing molecules. To provide a novel means of studying such "electrostatic competition" effects, computer simulation methodology has been developed to allow the diffusion and association of many solute molecules around a single enzyme to be simulated. Although the idea that electrostatic potentials generated by enzymes can guide substrates to active sites is well established, it is not always appreciated that the same potentials can also promote the binding of molecules other than the intended substrate, with the result that such enzymes might be sensitive to the presence of competing molecules. To provide a novel means of studying such "electrostatic competition" effects, computer simulation methodology has been developed to allow the diffusion and association of many solute molecules around a single enzyme to be simulated. To demonstrate the power of the methodology, simulations have been conducted on an artificial fusion protein of citrate synthase (CS) and malate dehydrogenase (MDH) to assess the chances of oxaloacetate being channeled between the MDH and CS active sites. The simulations demonstrate that the probability of channeling is strongly dependent on the concentration of the initial substrate (malate) in the solution. In fact, the high concentrations of malate used in experiments appear high enough to abolish any channeling of oxaloacetate. The simulations provide a resolution of a serious discrepancy between previous simulations and experiments and raise important questions relating to the observability of electrostatically mediated substrate channeling in vitro and in vivo. | |
| 650 | 2 | 2 | |a Binding Sites |
| 650 | 1 | 2 | |a Citrate (si)-Synthase |x chemistry |
| 650 | 2 | 2 | |a Citrate (si)-Synthase |x metabolism |
| 650 | 2 | 2 | |a Computer Simulation |
| 650 | 2 | 2 | |a Enzymes |x chemistry |
| 650 | 1 | 2 | |a Enzymes |x metabolism |
| 650 | 2 | 2 | |a Kinetics |
| 650 | 2 | 2 | |a Malates |x chemistry |
| 650 | 2 | 2 | |a Models, Molecular |
| 650 | 2 | 2 | |a Models, Theoretical |
| 650 | 2 | 2 | |a Osmolar Concentration |
| 650 | 2 | 2 | |a Protein Conformation |
| 650 | 2 | 2 | |a Recombinant Fusion Proteins |x chemistry |
| 650 | 2 | 2 | |a Recombinant Fusion Proteins |x metabolism |
| 650 | 2 | 2 | |a Static Electricity |
| 650 | 2 | 2 | |a Substrate Specificity |
| 653 | |a Molecules | ||
| 653 | |a Computer based modeling | ||
| 653 | |a Environmental | ||
| 773 | 0 | |t Biophysical Journal |g vol. 82, no. 5 (May 2002), p. 2326-2332 | |
| 786 | 0 | |d ProQuest |t Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/215711044/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text + Graphics |u https://www.proquest.com/docview/215711044/fulltextwithgraphics/embedded/6A8EOT78XXH2IG52?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/215711044/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch |