CAMP-dependent protein kinase

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<StructureSection load='1xh6' size='350' side='right' scene='46/468128/Cv/1' caption='Bovine PKA catalytic subunit (magenta) complex with PKA inhibitor (green) and nicotinamide derivative (PDB code [[1xh6]])'>
<StructureSection load='1xh6' size='350' side='right' scene='46/468128/Cv/1' caption='Bovine PKA catalytic subunit (magenta) complex with PKA inhibitor (green) and nicotinamide derivative (PDB code [[1xh6]])'>
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__TOC__
== Function ==
== Function ==
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* [[Eukaryotic Protein Kinase Catalytic Domain]]
* [[Eukaryotic Protein Kinase Catalytic Domain]]
* [[Protein Kinase A]].
* [[Protein Kinase A]].
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* [[CAMP-dependent pathway]].
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* [[CAMP is second messenger]].
== Structural highlights ==
== Structural highlights ==
In the absence of cAMP, PKA is an inactive tetramer with 2 catalytic subunits and 2 regulatory subunits. The regulatory subunit contains inhibitory region, two cAMP-binding domains and a C-terminal dimerization domain. The catalytic subunit contains an ATP-binding domain and a regulatory subunit binding domain.
In the absence of cAMP, PKA is an inactive tetramer with 2 catalytic subunits and 2 regulatory subunits. The regulatory subunit contains inhibitory region, two cAMP-binding domains and a C-terminal dimerization domain. The catalytic subunit contains an ATP-binding domain and a regulatory subunit binding domain.
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*<scene name='46/468128/Cv/3'>cAMP-binding site of catalytic subunit</scene> ([[4ntt]]).<ref>PMID:25077557</ref>
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*<scene name='46/468128/Cv/6'>cAMP-binding site of catalytic subunit</scene> ([[4ntt]]).<ref>PMID:25077557</ref>
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*<scene name='46/468128/Cv/5'>Bovine PKA I-alpha ATP-binding pocket</scene> ([[4jv4]]).<ref>PMID:23978166</ref>
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*<scene name='46/468128/Cv/7'>Bovine PKA I-alpha ATP-binding pocket</scene> ([[4jv4]]).<ref>PMID:23978166</ref>
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</StructureSection>
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==3D structures of cAMP-dependent protein kinase==
==3D structures of cAMP-dependent protein kinase==
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[[CAMP-dependent protein kinase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*'''PKA catalytic subunit'''
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**[[1j3h]] – mPKA – mouse
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**[[1syk]], [[4dfy]], [[4nts]] - mPKA (mutant)
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**[[1fot]] - yPKA – yeast<br />
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**[[4ae6]], [[4ae9]] – hPKA 2 – human<br />
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*PKA catalytic subunit binary complex
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**[[2cpk]], [[1ctp]], [[1fmo]], [[1l3r]], [[1xh4]], [[1xh5]], [[1xh6]], [[1xh7]], [[1xh8]], [[1xh9]], [[1xha]], [[3fjq]], [[4dg0]], [[4dg2]], [[4dh1]], [[4dh3]], [[4dh5]], [[4dh7]], [[4dh8]], [[4hpt]], [[4hpu]] – mPKA + peptide inhibitor<br />
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**[[1q61]], [[1q62]], [[1smh]], [[2qur]], [[3qal]], [[3qam]], [[4dfx]], [[4dfz]], [[4dg3]] - mPKA (mutant) + peptide inhibitor<br />
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**[[4iac]], [[4iad]], [[4iaf]], [[4iai]], [[4iak]], [[4iay]], [[4iaz]], [[4ib0]], [[4ib1]], [[4ib3]], [[4o22]] – mPKA + SP20 peptide<br />
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**[[4ntt]] – mPKA (mutant) + ADP<br />
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**[[2gfc]], [[3dnd]], [[3dne]], [[3kkv]], [[3zo1]], [[3zo2]], [[3zo3]], [[3zo4]], [[4ie9]], [[4ij9]] - bPKA + peptide inhibitor<br />
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**[[4wih]] - PKA + peptide inhibitor – hamster<br />
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**[[2gng]], [[4axa]], [[4c33]], [[4c34]], [[4c35]], [[4c36]], [[4c37]], [[4c38]] - bPKA (mutant) + peptide inhibitor<br />
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**[[3mvj]], [[3oog]], [[3poo]], [[3vqh]] - hPKA + peptide inhibitor<br />
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**[[4wb5]], [[4wb6]], [[4wb8]] – mPKA (mutant) + PKI peptide<br />
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**[[3bwj]] - bPKA + bisubstrate inhibitor<br />
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**[[3agl]], [[3agm]] – hPKA + bisubstrate inhibitor<br />
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**[[1bkx]] – mPKA + adenosine<br />
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**[[3o7l]] – mPKA + phospholamban<br />
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**[[1bx6]], [[1re8]], [[1rej]], [[1rek]] - mPKA + balanol analog<br />
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**[[1cdk]] - pPKA + peptide inhibitor – pig<br />
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**[[1szm]] - bPKA + bisindolymaleimide<br />
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**[[3ag9]] - bPKA + inhibitor<br />
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*PKA catalytic subunit ternary complex
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**[[1apm]], [[1jlu]] - mPKA + detergent + peptide inhibitor<br />
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**[[1jbp]] - mPKA + detergent + peptide inhibitor + ADP<br />
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**[[1rdq]] - mPKA + peptide inhibitor + ADP + ATP<br />
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**[[1atp]] - mPKA + peptide inhibitor + Mn-ATP<br />
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**[[2erz]] - mPKA + peptide inhibitor + hydroxyfasudil<br />
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**[[1cmk]] - pPKA + peptide inhibitor + myristic acid<br />
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**[[1stc]] - bPKA + peptide inhibitor + saturosporine<br />
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**[[2gnh]], [[2gni]], [[2gnj]], [[2gnl]], [[2jdv]], [[2uvx]], [[2uvy]], [[2uvz]], [[2uw0]], [[2uw3]], [[2uw4]], [[2uw5]], [[2uw6]], [[2uw7]], [[2uw8]], [[2vnw]], [[2vny]], [[2vo0]], [[2vo3]], [[2vo6]], [[2vo7]] - bPKA (mutant) + peptide inhibitor + inhibitor<br />
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**[[1ydr]], [[1yds]], [[1ydt]] - bPKA + peptide inhibitor + inhibitor<br />
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**[[2gu8]], [[3l9l]], [[3ovv]], [[3owp]], [[3oxt]], [[3p0m]] - hPKA catalytic subunit + peptide inhibitor + inhibitor<br />
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**[[3nx8]] - hPKA catalytic subunit + peptide inhibitor + phenol<br />
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**[[3l9m]], [[3l9n]], [[3ama]], [[3amb]] - hPKA (mutant) + peptide inhibitor + inhibitor<br />
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**[[3ow3]] - mPKA catalytic subunit + peptide inhibitor + inhibitor<br />
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**[[2f7e]], [[2f7x]], [[2f7z]], [[2jds]] - bPKA catalytic subunit + peptide inhibitor + inhibitor<br />
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**[[3e8c]], [[3e8e]] - bPKA catalytic subunit + peptide inhibitor + ATP-competitive inhibitor<br />
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**[[1q24]] - bPKA + peptide inhibitor + Mg-ATP<br />
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**[[1q8t]], [[1q8u]], [[1q8w]]- bPKA + peptide inhibitor + rho-kinase inhibitor<br />
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**[[2gnf]] - bPKA (mutant) + peptide inhibitor + rho-kinase inhibitor<br />
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**[[1sve]], [[1svg]], [[1svh]], [[1veb]] - bPKA + detergent + peptide inhibitor + azepane derivative<br />
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**[[2c1a]], [[2c1b]] - bPKA + peptide inhibitor + isoquinoline-sulfamide inhibitor<br />
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**[[2oh0]], [[2ojf]] - bPKA + peptide inhibitor + pyridine-pyrazolopyridine inhibitor<br />
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**[[2uzt]], [[2uzu]], [[2uzv]], [[2uzw]] - bPKA + peptide inhibitor + indazole-pyridine inhibitor<br />
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**[[2jdt]] - bPKA (mutant) + peptide inhibitor + isoquinoline-sulfamide inhibitor<br />
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*PKA regulatory subunit
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**[[1cx4]] - rPKA II-β cAMP-binding domain – rat<br />
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**[[1r2a]] - mPKA II dimerization-anchoring domain – NMR<br />
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**[[1l6e]] - mPKA II-α dimerization-anchoring domain – NMR<br />
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**[[2ezw]] - bPKA I-α dimerization-anchoring domain – bovine - NMR<br />
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**[[1ne4]], [[1ne6]], [[1rl3]], [[3iia]], [[1rgs]], [[4mx3]] - bPKA <br />
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**[[3im3]] - bPKA I-α dimerization-anchoring domain<br />
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**[[3pna]] - bPKA I-α cAMP-binding domain<br />
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**[[3of1]] - yPKA <br />
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**[[4f9k]] – hPKA I-β<br />
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*PKA regulatory subunit binary complex
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**[[2drn]], [[2h9r]] - rPKA II-α dimerization-anchoring domain + A-kinase anchoring protein peptide – NMR<br />
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**[[2izx]], [[2izy]] - hPKA II-α + A-kinase anchoring protein peptide<br />
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**[[3im4]] - bPKA I-α + A-kinase anchoring protein peptide<br />
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**[[2hwn]] - rPKA II-α + A-kinase binding peptide<br />
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**[[4jva]] – rPKA II-β + cAMP analog<br />
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**[[4jv4]] – bPKA I-α + cAMP analog<br />
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**[[2kyg]] - hPKA II-α + CBFA2T1<br />
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**[[3plq]] - bPKA I-α + cAMP derivative<br />
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*PKA regulatory subunit ternary complex
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**[[3tmh]] - rPKA II-α dimerization-anchoring domain + A-kinase anchoring protein peptide + NHERF-3<br />
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*PKA catalytic and regulatory subunits
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**[[2qvs]], [[3idb]], [[3idc]], [[3pvb]], [[4din]] - mPKA <br />
 
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**[[3fhi]], [[2qcs]], [[3tnp]], [[3tnq]] - mPKA (mutant) <br />
 
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**[[3j4q]], [[3j4r]] – mPKA + A-kinase anchor protein 18<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Bovine PKA catalytic subunit (magenta) complex with PKA inhibitor (green) and nicotinamide derivative (PDB code 1xh6)

Drag the structure with the mouse to rotate

References

  1. ↑ Bastidas AC, Wu J, Taylor SS. Molecular Features of Product Release for the PKA Catalytic Cycle. Biochemistry. 2014 Aug 8. PMID:25077557 doi:http://dx.doi.org/10.1021/bi500684c
  2. ↑ Brown SH, Cheng CY, Saldanha SA, Wu J, Cottam HB, Sankaran B, Taylor SS. Implementing Fluorescence Anisotropy Screening and Crystallographic Analysis to Define PKA Isoform-Selective Activation by cAMP Analogs. ACS Chem Biol. 2013 Sep 10. PMID:23978166 doi:10.1021/cb400247t

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

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