1cdk
From Proteopedia
(New page: 200px<br /><applet load="1cdk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cdk, resolution 2.0Å" /> '''CAMP-DEPENDENT PROTEI...) |
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| - | [[Image:1cdk.gif|left|200px]]<br /><applet load="1cdk" size=" | + | [[Image:1cdk.gif|left|200px]]<br /><applet load="1cdk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1cdk, resolution 2.0Å" /> | caption="1cdk, resolution 2.0Å" /> | ||
'''CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT (E.C.2.7.1.37) (PROTEIN KINASE A) COMPLEXED WITH PROTEIN KINASE INHIBITOR PEPTIDE FRAGMENT 5-24 (PKI(5-24) ISOELECTRIC VARIANT CA) AND MN2+ ADENYLYL IMIDODIPHOSPHATE (MNAMP-PNP) AT PH 5.6 AND 7C AND 4C'''<br /> | '''CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT (E.C.2.7.1.37) (PROTEIN KINASE A) COMPLEXED WITH PROTEIN KINASE INHIBITOR PEPTIDE FRAGMENT 5-24 (PKI(5-24) ISOELECTRIC VARIANT CA) AND MN2+ ADENYLYL IMIDODIPHOSPHATE (MNAMP-PNP) AT PH 5.6 AND 7C AND 4C'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the porcine heart catalytic subunit of | + | The crystal structure of the porcine heart catalytic subunit of cAMP-dependent protein kinase in a ternary complex with the MgATP analogue MnAMP-PNP and a pseudosubstrate inhibitor peptide, PKI(5-24), has been solved at 2.0 A resolution from monoclinic crystals of the catalytic subunit isoform CA. The refinement is presently at an R factor of 0.194 and the active site of the molecule is well defined. The glycine-rich phosphate anchor of the nucleotide binding fold motif of the protein kinase is a beta ribbon acting as a flap with conformational flexibility over the triphosphate group. The glycines seem to be conserved to avoid steric clash with ATP. The known synergistic effects of substrate binding can be explained by hydrogen bonds present only in the ternary complex. Implications for the kinetic scheme of binding order are discussed. The structure is assumed to represent a phosphotransfer competent conformation. The invariant conserved residue Asp166 is proposed to be the catalytic base and Lys168 to stabilize the transition state. In some tyrosine kinases Lys168 is functionally replaced by an Arg displaced by two residues in the primary sequence, suggesting invariance in three-dimensional space. The structure supports an in-line transfer with a pentacoordinate transition state at the phosphorus with very few nuclear movements. |
==About this Structure== | ==About this Structure== | ||
| - | 1CDK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with PO3, MN, ANP and MYR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1CDK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=PO3:'>PO3</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=ANP:'>ANP</scene> and <scene name='pdbligand=MYR:'>MYR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CDK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Bossemeyer, D.]] | [[Category: Bossemeyer, D.]] | ||
| - | [[Category: Engh, R | + | [[Category: Engh, R A.]] |
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
[[Category: Kinzel, V.]] | [[Category: Kinzel, V.]] | ||
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[[Category: complex (transferase/inhibitor)]] | [[Category: complex (transferase/inhibitor)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:05:04 2008'' |
Revision as of 10:05, 21 February 2008
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CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT (E.C.2.7.1.37) (PROTEIN KINASE A) COMPLEXED WITH PROTEIN KINASE INHIBITOR PEPTIDE FRAGMENT 5-24 (PKI(5-24) ISOELECTRIC VARIANT CA) AND MN2+ ADENYLYL IMIDODIPHOSPHATE (MNAMP-PNP) AT PH 5.6 AND 7C AND 4C
Overview
The crystal structure of the porcine heart catalytic subunit of cAMP-dependent protein kinase in a ternary complex with the MgATP analogue MnAMP-PNP and a pseudosubstrate inhibitor peptide, PKI(5-24), has been solved at 2.0 A resolution from monoclinic crystals of the catalytic subunit isoform CA. The refinement is presently at an R factor of 0.194 and the active site of the molecule is well defined. The glycine-rich phosphate anchor of the nucleotide binding fold motif of the protein kinase is a beta ribbon acting as a flap with conformational flexibility over the triphosphate group. The glycines seem to be conserved to avoid steric clash with ATP. The known synergistic effects of substrate binding can be explained by hydrogen bonds present only in the ternary complex. Implications for the kinetic scheme of binding order are discussed. The structure is assumed to represent a phosphotransfer competent conformation. The invariant conserved residue Asp166 is proposed to be the catalytic base and Lys168 to stabilize the transition state. In some tyrosine kinases Lys168 is functionally replaced by an Arg displaced by two residues in the primary sequence, suggesting invariance in three-dimensional space. The structure supports an in-line transfer with a pentacoordinate transition state at the phosphorus with very few nuclear movements.
About this Structure
1CDK is a Protein complex structure of sequences from Oryctolagus cuniculus and Sus scrofa with , , and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24)., Bossemeyer D, Engh RA, Kinzel V, Ponstingl H, Huber R, EMBO J. 1993 Mar;12(3):849-59. PMID:8384554
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