1syk
From Proteopedia
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| - | [[Image:1syk.gif|left|200px]] | + | [[Image:1syk.gif|left|200px]] |
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| - | '''Crystal structure of E230Q mutant of cAMP-dependent protein kinase reveals unexpected apoenzyme conformation''' | + | {{Structure |
| + | |PDB= 1syk |SIZE=350|CAPTION= <scene name='initialview01'>1syk</scene>, resolution 2.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | ||
| + | |GENE= PRKACA, PKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of E230Q mutant of cAMP-dependent protein kinase reveals unexpected apoenzyme conformation''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SYK is a [ | + | 1SYK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SYK OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix., Wu J, Yang J, Kannan N, Madhusudan, Xuong NH, Ten Eyck LF, Taylor SS, Protein Sci. 2005 Nov;14(11):2871-9. PMID:[http:// | + | Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix., Wu J, Yang J, Kannan N, Madhusudan, Xuong NH, Ten Eyck LF, Taylor SS, Protein Sci. 2005 Nov;14(11):2871-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16253959 16253959] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: e230q mutant; catalytic subunit; camp-dependent protein kinase; apoenzyme conformation; n-terminal a-helix]] | [[Category: e230q mutant; catalytic subunit; camp-dependent protein kinase; apoenzyme conformation; n-terminal a-helix]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:11:18 2008'' |
Revision as of 12:11, 20 March 2008
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| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | PRKACA, PKACA (Mus musculus) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of E230Q mutant of cAMP-dependent protein kinase reveals unexpected apoenzyme conformation
Overview
Glu230, one of the acidic residues that cluster around the active site of the catalytic subunit of cAMP-dependent protein kinase, plays an important role in substrate recognition. Specifically, its side chain forms a direct salt-bridge interaction with the substrate's P-2 Arg. Previous studies showed that mutation of Glu230 to Gln (E230Q) caused significant decreases not only in substrate binding but also in the rate of phosphoryl transfer. To better understand the importance of Glu230 for structure and function, we solved the crystal structure of the E230Q mutant at 2.8 A resolution. Surprisingly, the mutant preferred an open conformation with no bound ligands observed, even though the crystals were grown in the presence of MgATP and the inhibitor peptide, IP20. This is in contrast to the wild-type protein that, under the same conditions, prefers the closed conformation of a ternary complex. The structure highlights the importance of the electrostatic surface not only for substrate binding and catalysis, but also for the mechanism for closing the active site cleft. This surface mutation clearly disrupts the recognition and binding of substrate peptide so that the enzyme prefers an open conformation that cannot trap ATP. This is consistent with the reinforcing concepts of conformational dynamics and the synergistic binding of ATP and substrate peptide. Another unusual feature of the structure is the observation of the entire N terminus (Gly1-Thr32) assumes an extended alpha-helix conformation. Finally, based on temperature factors, this mutant structure is more stable than the wild-type C-subunit in the apo state.
About this Structure
1SYK is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix., Wu J, Yang J, Kannan N, Madhusudan, Xuong NH, Ten Eyck LF, Taylor SS, Protein Sci. 2005 Nov;14(11):2871-9. PMID:16253959
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