dorsal/arxiv
View SchemaConformational Dependence of a Protein Kinase Phosphate Transfer Reaction
| Authors | Graeme Henkelman, Montiago X. LaBute, Chang-Shung Tung, P. W. Fenimore, Benjamin H. McMahon |
|---|---|
| Categories | |
| ArXiv ID | physics/0406044 |
| URL | https://arxiv.org/abs/physics/0406044 |
| DOI | 10.1073/pnas.0506425102 |
Abstract
Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase (PKA) are calculated by plane-wave density functional theory, starting from structures of proteins crystallized in both the reactant conformation (RC) and the transition-state conformation (TC). In the TC, we calculate that the reactants and products are nearly isoenergetic with a 0.2 eV barrier; while phosphate transfer is unfavorable by over 1.2 eV in the RC, with an even higher barrier. With the protein in the TC, the motions involved in reaction are small, with only P$_\gamma$ and the catalytic proton moving more than 0.5 \AA. Examination of the structures reveals that in the RC the active site cleft is not completely closed and there is insufficient space for the phosphorylated serine residue in the product state. Together, these observations imply that the phosphate transfer reaction occurs rapidly and reversibly in a particular conformation of the protein, and that the reaction can be gated by changes of a few tenths of an \AA in the catalytic site.
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"abstract": "Atomic motions and energetics for a phosphate transfer reaction catalyzed by\nthe cAMP-dependent protein kinase (PKA) are calculated by plane-wave density\nfunctional theory, starting from structures of proteins crystallized in both\nthe reactant conformation (RC) and the transition-state conformation (TC). In\nthe TC, we calculate that the reactants and products are nearly isoenergetic\nwith a 0.2 eV barrier; while phosphate transfer is unfavorable by over 1.2 eV\nin the RC, with an even higher barrier. With the protein in the TC, the motions\ninvolved in reaction are small, with only P$_\\gamma$ and the catalytic proton\nmoving more than 0.5 \\AA. Examination of the structures reveals that in the RC\nthe active site cleft is not completely closed and there is insufficient space\nfor the phosphorylated serine residue in the product state. Together, these\nobservations imply that the phosphate transfer reaction occurs rapidly and\nreversibly in a particular conformation of the protein, and that the reaction\ncan be gated by changes of a few tenths of an \\AA in the catalytic site.",
"arxiv_id": "physics/0406044",
"authors": [
"Graeme Henkelman",
"Montiago X. LaBute",
"Chang-Shung Tung",
"P. W. Fenimore",
"Benjamin H. McMahon"
],
"categories": [
"physics.chem-ph",
"physics.bio-ph"
],
"doi": "10.1073/pnas.0506425102",
"title": "Conformational Dependence of a Protein Kinase Phosphate Transfer Reaction",
"url": "https://arxiv.org/abs/physics/0406044"
},
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