Solvent effects on allosteric equilibria : stabilization of T and R conformations of Escherichia coli aspartate transcarbamylase by organic solvents
The activity of Escherichia coli aspartate transcarbamylase (ATCase) is markedly influenced by the addition of organic solvents to the assay medium. The cosolvents tested, which include simple aliphatic alcohols, amides, and ureas, as well as acetone and dioxane, fall into two different classes: the most polar ones (formamide, acetamide, N-methylformamide, and urea) stimulate the enzyme activity for all concentrations tested. In contrast, solvents that are less polar than water inhibit the enzyme at low concentrations but stimulate it at higher concentrations. No comparable effects are observed in the case of the isolated catalytic subunits, a non-regulated form of ATCase. Extensive kinetic studies on ATCase and on two of its Michaelian derivatives, 2-thioU-ATCase and carbamylated ATCase, indicate that solvents modulate the same allosteric transition that is responsible for homotropic interactions between the catalytic sites. The stabilization of the R state of ATCase by comparatively high concentrations of cosolvents is reminiscent of similar findings made on hemoglobin and glycogen phosphorylase, suggesting a common underlying mechanism. Addition of organic cosolvents to water is known to reduce hydrophobic interactions, and we suggest that this effect may preferentially stabilize the more "relaxed" conformations of allosteric proteins, because they have a larger surface exposed to solvent [Chothia, C. (1974) Nature (London) 248, 338-339]. On the other hand, we suggest that the stabilization of the T state by low concentrations of all but the most polar cosolvents simply reflects stronger electrostatic interactions in this conformation.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1984 |
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| Erschienen: |
1984 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Biochemistry - 23(1984), 21 vom: 09. Okt., Seite 4852-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dreyfus, M [VerfasserIn] |
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| Themen: |
Aspartate Carbamoyltransferase |
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| Anmerkungen: |
Date Completed 14.01.1985 Date Revised 13.06.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM063656388 |
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| 100 | 1 | |a Dreyfus, M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Solvent effects on allosteric equilibria |b stabilization of T and R conformations of Escherichia coli aspartate transcarbamylase by organic solvents |
| 264 | 1 | |c 1984 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 14.01.1985 | ||
| 500 | |a Date Revised 13.06.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The activity of Escherichia coli aspartate transcarbamylase (ATCase) is markedly influenced by the addition of organic solvents to the assay medium. The cosolvents tested, which include simple aliphatic alcohols, amides, and ureas, as well as acetone and dioxane, fall into two different classes: the most polar ones (formamide, acetamide, N-methylformamide, and urea) stimulate the enzyme activity for all concentrations tested. In contrast, solvents that are less polar than water inhibit the enzyme at low concentrations but stimulate it at higher concentrations. No comparable effects are observed in the case of the isolated catalytic subunits, a non-regulated form of ATCase. Extensive kinetic studies on ATCase and on two of its Michaelian derivatives, 2-thioU-ATCase and carbamylated ATCase, indicate that solvents modulate the same allosteric transition that is responsible for homotropic interactions between the catalytic sites. The stabilization of the R state of ATCase by comparatively high concentrations of cosolvents is reminiscent of similar findings made on hemoglobin and glycogen phosphorylase, suggesting a common underlying mechanism. Addition of organic cosolvents to water is known to reduce hydrophobic interactions, and we suggest that this effect may preferentially stabilize the more "relaxed" conformations of allosteric proteins, because they have a larger surface exposed to solvent [Chothia, C. (1974) Nature (London) 248, 338-339]. On the other hand, we suggest that the stabilization of the T state by low concentrations of all but the most polar cosolvents simply reflects stronger electrostatic interactions in this conformation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Macromolecular Substances |2 NLM | |
| 650 | 7 | |a Solvents |2 NLM | |
| 650 | 7 | |a Aspartate Carbamoyltransferase |2 NLM | |
| 650 | 7 | |a EC 2.1.3.2 |2 NLM | |
| 700 | 1 | |a Fries, J |e verfasserin |4 aut | |
| 700 | 1 | |a Tauc, P |e verfasserin |4 aut | |
| 700 | 1 | |a Hervé, G |e verfasserin |4 aut | |
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