Protein/solvent medium effects on Mg(2+)-carboxylate interactions in metalloenzymes
We employed umbrella sampling molecular dynamics simulations in explicit water to study the binding of the Mg(2+) cofactor to ribonuclease H (RNase H) from three different organisms. We show that the enzyme can differentiate between different Mg(2+)-binding modes that are nearly equally stable by cr...
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| Veröffentlicht in: | Journal of the American Chemical Society 2010-05, Vol.132 (18), p.6290-6291 |
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| container_title | Journal of the American Chemical Society |
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| creator | Babu, C Satheesan Lim, Carmay |
| description | We employed umbrella sampling molecular dynamics simulations in explicit water to study the binding of the Mg(2+) cofactor to ribonuclease H (RNase H) from three different organisms. We show that the enzyme can differentiate between different Mg(2+)-binding modes that are nearly equally stable by creating a free-energy barrier between a water-rich mode and a water-depleted mode. Through a comparison with the corresponding free-energy barrier in water, this effect is shown to emanate from the enzymes's three-dimensional architecture and its associated environment. Implications of these protein medium effects in RNase H function and in structure-based drug/molecular design are discussed. |
| doi_str_mv | 10.1021/ja101494m |
| format | Article |
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We show that the enzyme can differentiate between different Mg(2+)-binding modes that are nearly equally stable by creating a free-energy barrier between a water-rich mode and a water-depleted mode. Through a comparison with the corresponding free-energy barrier in water, this effect is shown to emanate from the enzymes's three-dimensional architecture and its associated environment. 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| ispartof | Journal of the American Chemical Society, 2010-05, Vol.132 (18), p.6290-6291 |
| issn | 1520-5126 |
| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Binding Sites Carboxylic Acids - metabolism Drug Design Enzymes - chemistry Enzymes - metabolism Escherichia coli - enzymology HIV-1 - enzymology Leukemia Virus, Murine - enzymology Magnesium - metabolism Metalloproteins - chemistry Metalloproteins - metabolism Models, Molecular Protein Binding Protein Conformation Ribonuclease H - chemistry Ribonuclease H - metabolism Solvents - chemistry Thermodynamics Water - chemistry |
| title | Protein/solvent medium effects on Mg(2+)-carboxylate interactions in metalloenzymes |
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