User:Alice Harmon/Sandbox 1
From Proteopedia
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'''Eukaryotic Protein Kinase Catalytic Domain''' | '''Eukaryotic Protein Kinase Catalytic Domain''' | ||
| - | Eukaryotic protein kinases are enzymes that transfer a phosphoryl group (-PO<sub>3</sub><sup>2-</sup>) from adenosine triphosphate (or more rarely from adenosine diphosphate) to the hydroxyl group of serine, threonine, or tyrosine residue of a protein substrate. Phosphorylation of the substrate can affect its activity and/or conformation and, in turn, the physiogy of the cell. Protein kinases act as switches that turn on or off metabolic and signaling pathways, and they play central roles in development, responses to the environment, and in diseases such as cancer. The number of protein kinase genes (and the percentage of the genome) for bakers yeast <ref>PMID: 9020587</ref>, humans <ref> PMID:12471243</ref> and rice <ref>PMID:17172291</ref> | + | Eukaryotic protein kinases are enzymes that transfer a phosphoryl group (-PO<sub>3</sub><sup>2-</sup>) from adenosine triphosphate (or more rarely from adenosine diphosphate) to the hydroxyl group of serine, threonine, or tyrosine residue of a protein substrate. Phosphorylation of the substrate can affect its activity and/or conformation and, in turn, the physiogy of the cell. Protein kinases act as switches that turn on or off metabolic and signaling pathways, and they play central roles in development, responses to the environment, and in diseases such as cancer. The number of protein kinase genes (and the percentage of the genome) for bakers yeast <ref>PMID: 9020587</ref>, humans <ref> PMID:12471243</ref> and rice <ref>PMID:17172291</ref> are 113 (2%),518 (2%), and 1429 (5%), respectively. The catalytic domains of these enzymes occur alone or with other functional domains in a single polypetide chain. Protein kinases may be monomeric or multimeric or found in complexes with regulatory protiens. |
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| - | + | This article describes the general structure of protein kinase domains. It is based on the analysis of the primary structure of protein kinases by Hanks, Quinn, and Hunter <ref> PMID: 3291115</ref> in which the amino acid sequences of 65 protein kinases were aligned, and the revised analysis by Hanks and Hunter <ref> PMID: 7768349</ref>, and on the first three-dimensional structure of protein kinase to be published, that of PKA by Knighton et al. <ref> PMID: 1862342<?ref>. The results described in these papers apply to the basic structure of the great range of eukaryotic protein kinases known today. | |
| - | + | The crystal structure 1ATP shows that catalytic domains of eukaryotic protein kinases have a small lobe and a large lobe (seen at the top and bottom of the model in the scene, respectively), and the catalytic site is located in a cleft between them. The small lobe binds ATP and the large lobe binds the protein substrate. The crystal structure includes ATP<sup>.</sup>2Mg<sup>2+</sup> and the inhibitor peptide that has an alanine substituted for serine in a substrate's phosphorylation motif RRxS. All of the molecular scenes below include ATP, and some include the inhibitor peptide to illustrate kinase/substrate interactions. | |
| - | + | Following is a tour of the twelve conserved subdomains (numbered starting at the amino terminal end of the catalytic domain) defined by Hanks and Hunter using 1PKA as a model. | |
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<Structure load='1ATP' size='500' frame='true' align='right' caption='1PKA - Protein kinase A in complex with ATP, magnesium and inhibitor peptide' scene='Insert optional scene name here' /> | <Structure load='1ATP' size='500' frame='true' align='right' caption='1PKA - Protein kinase A in complex with ATP, magnesium and inhibitor peptide' scene='Insert optional scene name here' /> | ||
Revision as of 18:10, 20 August 2013
Eukaryotic Protein Kinase Catalytic Domain
Eukaryotic protein kinases are enzymes that transfer a phosphoryl group (-PO32-) from adenosine triphosphate (or more rarely from adenosine diphosphate) to the hydroxyl group of serine, threonine, or tyrosine residue of a protein substrate. Phosphorylation of the substrate can affect its activity and/or conformation and, in turn, the physiogy of the cell. Protein kinases act as switches that turn on or off metabolic and signaling pathways, and they play central roles in development, responses to the environment, and in diseases such as cancer. The number of protein kinase genes (and the percentage of the genome) for bakers yeast [1], humans [2] and rice [3] are 113 (2%),518 (2%), and 1429 (5%), respectively. The catalytic domains of these enzymes occur alone or with other functional domains in a single polypetide chain. Protein kinases may be monomeric or multimeric or found in complexes with regulatory protiens.
This article describes the general structure of protein kinase domains. It is based on the analysis of the primary structure of protein kinases by Hanks, Quinn, and Hunter [4] in which the amino acid sequences of 65 protein kinases were aligned, and the revised analysis by Hanks and Hunter [5], and on the first three-dimensional structure of protein kinase to be published, that of PKA by Knighton et al. [6]
