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| - | [[Image:1rdq.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1rdq| PDB=1rdq | SCENE= }} | | {{STRUCTURE_1rdq| PDB=1rdq | SCENE= }} |
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| - | '''Hydrolysis of ATP in the crystal of Y204A mutant of cAMP-dependent protein kinase'''
| + | ===Hydrolysis of ATP in the crystal of Y204A mutant of cAMP-dependent protein kinase=== |
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| - | ==Overview==
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| - | The catalytic subunit of cAMP-dependent protein kinase has served as a paradigm for the entire kinase family. In the course of studying the structure-function relationship of the P+1 loop (Leu198-Leu205) of the kinase, we have solved the crystal structure of the Tyr204 to Ala mutant in complexes with Mg.ATP and an inhibitory peptide at 1.26A, with overall structure very similar to that of the wild-type protein. However, at the nucleotide binding site, ATP was found largely hydrolyzed, with the products ADP-PO(4) retained in the structure. High-resolution refinement suggests that 26% of the molecules contain the intact ATP, whereas 74% have the hydrolyzed products. The observation of the substrate and product states in the same structure adds significant information to our understanding of the phosphoryl transfer process. Structural examination of the mutation site substantiates and extends the emerging concept that the hydrophobic core in the large lobe of the kinase might serve as a stable platform for anchoring key segments involved in catalysis. We propose that Tyr204 is critical for anchoring the P+1 loop to the core. Further analysis has highlighted two major connections between the P+1 loop and the catalytic loop (Arg165-Asn171). One emphasizes the hydrophobic packing of Tyr204 and Leu167 mediated through residues from the alphaF-helix, recently recognized as a signal integration motif, which together with the alphaE-helix forms the center of the hydrophobic core network. The other connection is mediated by the hydrogen bond interaction between Thr201 and Asp166, in a substrate-dependent manner. We speculate that the latter interaction may be important for the kinase to sense the presence of substrate and prepare itself for the catalytic reaction. Thus, the P+1 loop is not merely involved in substrate binding; it mediates the communication between substrate and catalytic residues. | + | The line below this paragraph, {{ABSTRACT_PUBMED_14757059}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14757059 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_14757059}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Camp-dependent protein kinase,catalytic mechanism]] | | [[Category: Camp-dependent protein kinase,catalytic mechanism]] |
| | [[Category: Two nucleotide state]] | | [[Category: Two nucleotide state]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:22:13 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:46:22 2008'' |
Revision as of 04:46, 28 July 2008
Template:STRUCTURE 1rdq
Hydrolysis of ATP in the crystal of Y204A mutant of cAMP-dependent protein kinase
Template:ABSTRACT PUBMED 14757059
About this Structure
1RDQ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: new insights into the catalytic mechanism., Yang J, Ten Eyck LF, Xuong NH, Taylor SS, J Mol Biol. 2004 Feb 13;336(2):473-87. PMID:14757059
Page seeded by OCA on Mon Jul 28 07:46:22 2008
