User:Alice Harmon/Sandbox 1: Difference between revisions
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'''Protein Kinase''' | '''Protein Kinase''' | ||
Role as switches in the regulation of metabolic, and signaling pathways. Important in development, responses to the environment, and in diseases such as cancer. | |||
Two lobes, catalytic cleft. | |||
Hanks, Quinn, and Hunter and Taylor's work on PKA have provided | |||
<Structure load='1ATP' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='1ATP' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
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<scene name='55/555705/Lysine/2'>invariant lysine (ball and stick)</scene> that interacts with the phosphates of ATP. | <scene name='55/555705/Lysine/2'>invariant lysine (ball and stick)</scene> that interacts with the phosphates of ATP. | ||
<scene name='55/555705/Subdomainiii/1'>Subdomain III</scene> connects to many parts of the kinase and its orientation is critical for activity. In the active conformation of the kinase the invariant | <scene name='55/555705/Subdomainiii/1'>Subdomain III</scene> is an alpha helix (helix C in bovine PKA) that connects to many parts of the kinase, and its orientation is critical for activity. In the active conformation of the kinase the invariant | ||
<scene name='55/555705/Kesaltbridge/1'>nearly invariant glutamate (blue ball and stick) </scene> in Subdomain III forms a salt bridge with the invariant lysine of Subdomain II (yellow ball and stick). This salt bridge couples subdomain III to ATP. | <scene name='55/555705/Kesaltbridge/1'>nearly invariant glutamate (blue ball and stick) </scene> in Subdomain III forms a salt bridge with the invariant lysine of Subdomain II (yellow ball and stick). This salt bridge couples subdomain III to ATP. | ||
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<scene name='55/555705/Subdomainviii/1'>Subdomain VIII</scene> contains the APE motif. The <scene name='55/555705/Ape/1'>glutamate in this motif (blue ball and stick) </scene>glutamate in this motif forms a salt bridge with an arginine (yellow ball and stick) in in Subdomain X1. This salt bridge is critical for forming the stable kinase core. In many protein kinases there is a phosphorylatable residue seven to ten residues upstream of the APE motif. In PKA it is a <scene name='55/555705/Phosphothreonine/1'>phosphothreonine</scene> (blue ball and stick with the phosphate in CPK), which forms an ionic bond with the arginine (yellow ball and stick) in the HRDLKPEN motif of the catalytic loop and helps to position it for catalysis. Between the phosphorylated residue and the APE motif lies the <scene name='55/555705/Pplus1/1'>P+1 loop</scene> which interacts with the residue adjacent to the phosphorylated residue of the peptide substrate. | <scene name='55/555705/Subdomainviii/1'>Subdomain VIII</scene> contains the APE motif. The <scene name='55/555705/Ape/1'>glutamate in this motif (blue ball and stick) </scene>glutamate in this motif forms a salt bridge with an arginine (yellow ball and stick) in in Subdomain X1. This salt bridge is critical for forming the stable kinase core. In many protein kinases there is a phosphorylatable residue seven to ten residues upstream of the APE motif. In PKA it is a <scene name='55/555705/Phosphothreonine/1'>phosphothreonine</scene> (blue ball and stick with the phosphate in CPK), which forms an ionic bond with the arginine (yellow ball and stick) in the HRDLKPEN motif of the catalytic loop and helps to position it for catalysis. Between the phosphorylated residue and the APE motif lies the <scene name='55/555705/Pplus1/1'>P+1 loop</scene> which interacts with the residue adjacent to the phosphorylated residue of the peptide substrate. | ||
<scene name='55/555705/Subdomainix/1'>Subdomain IX</scene> | <scene name='55/555705/Subdomainix/1'>Subdomain IX</scene> is a very hydrophobic alpha helix (F in bovine PKA). | ||
<scene name='55/555705/Subdomainx/1'>Subdomain X</scene> and <scene name='55/555705/Subdomainxi/1'>Subdomain XI</scene> contain three alpha helices (G, H, and I in bovine PKA) that form the kinase core and which are involved in binding substrate proteins. | |||
<scene name='55/555705/ | Two hydrophobic spines are composed of amino acid residues that are non-contiguous in the primary structure.<scene name='55/555705/Spine1/1'> Spine 1 </scene>includes the adenine ring of ATP. In PKA the residues are A70, V57, ATP, L173, I174, L172, M128, M231, and L227. Spine two contains residues L106, L95, F185, Y164. Both of these spines are anchored to helix F (Subdomain IX). | ||
Revision as of 17:17, 19 August 2013
Protein Kinase
Role as switches in the regulation of metabolic, and signaling pathways. Important in development, responses to the environment, and in diseases such as cancer.
Two lobes, catalytic cleft.
Hanks, Quinn, and Hunter and Taylor's work on PKA have provided
|
contains two beta strands connected by the glycine rich ATP-binding loop with the motif shown in ball and stick.
contains an that interacts with the phosphates of ATP.
is an alpha helix (helix C in bovine PKA) that connects to many parts of the kinase, and its orientation is critical for activity. In the active conformation of the kinase the invariant in Subdomain III forms a salt bridge with the invariant lysine of Subdomain II (yellow ball and stick). This salt bridge couples subdomain III to ATP.
contains a beta strand and contributes to the core structure of the small lobe.
links the small and large lobes. It contributes residues to the and also for . In PKA Glu 127 (blue ball and stick) interacts with both the ribose of ATP and the first Arg (yellow ball and stick) in the phosphorylation motif RRxS of the peptide substrate.
is helix in the large lobe.
contains the catalytic loop with the conserved motif HRDLKxxN. The is the catalytic base that accepts the hydrogen removed from the hydroxyl group being phosphorylated. CHECK THIS FOR ACCURACY. Note the proximity of the glutamate residue to peptide residue that will be phosphorylated, here represented by an alanine (yellow ball and stick) in the inhibitor peptide.
, the Mg-binding loop with the DFG motif. The chelates a Mg2+ ion that bridges the gamma and beta phosphates of ATP and positions the gamma phosphate for transfer to the substrate.
the activation loop, the P+1 loop.
contains the APE motif. The glutamate in this motif forms a salt bridge with an arginine (yellow ball and stick) in in Subdomain X1. This salt bridge is critical for forming the stable kinase core. In many protein kinases there is a phosphorylatable residue seven to ten residues upstream of the APE motif. In PKA it is a (blue ball and stick with the phosphate in CPK), which forms an ionic bond with the arginine (yellow ball and stick) in the HRDLKPEN motif of the catalytic loop and helps to position it for catalysis. Between the phosphorylated residue and the APE motif lies the which interacts with the residue adjacent to the phosphorylated residue of the peptide substrate.
is a very hydrophobic alpha helix (F in bovine PKA).
and contain three alpha helices (G, H, and I in bovine PKA) that form the kinase core and which are involved in binding substrate proteins.
Two hydrophobic spines are composed of amino acid residues that are non-contiguous in the primary structure.includes the adenine ring of ATP. In PKA the residues are A70, V57, ATP, L173, I174, L172, M128, M231, and L227. Spine two contains residues L106, L95, F185, Y164. Both of these spines are anchored to helix F (Subdomain IX).