User:Alice Harmon/Sandbox 1: Difference between revisions

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3. These scenes show the alignments of structures critical for activity. The yellow Cα-trace is the DFG-activation loop sequence, the blue trace is the catalytic loop, and the orchid trace is the C-helix (subdomain III). In ball and stick are residues critical for catalytic activity: yellow is the D in DFG, which binds Mg<sup>2+</sup>; blue is the D in the YRDKLPEN, which is the catalytic base; cyan is the invariant K of subdomain II, which binds the phosphates of ATP; and orchid is the invariant E of subdomain III. The positions needed for catalysis can be seen in the closed, active kinase (left). The two D's and K are pointing toward ANP, and the E is bound to the K. The latter pulls the C-helix into position. In the open structure (middle) the elements of the large lobe are in place but the K of the small lobe is far away from the ANP binding site. Upon ATP binding the K interacts with the phosphates and the two lobes close. The view of the inactive structure (right) is oriented so that the backbones of the catalytic loop (blue) and ends of the activation loop (yellow) are positioned like those in the other two structures. The other residues of the activation loop are not shown because they were not resolved in the crystal structure because of their flexibility. The side chain of the D in the catalytic loop (blue ball and stick)points away from the ATP binding pocket, and the C-helix is rotated upward. The assembly of these elements depends on the phosphorylation of threonine 197 in the activation loop. The phosphate of the residue forms five critical bonds that align the active site structures<ref>PMID:22334660</ref>.

===Regulation of Protein Kinase Activity===

There are a variety of ways that the activity of protein kinases are regulated. Here are a few examples. Some are regulated via phosphorylation of residue(s) in the activation loop by either an upstream protein kinase (such as [[mitogen-activated protein kinase]] phosphorylation by MAPKK) or by autophosphosphorylation stimulated by the binding of a ligand (such as the insulin receptor kinase<ref>PMID:7997262</ref>). Others are activated by binding with other proteins, which brings the kinase into the active conformation. The PKA C subunit, having been constitutively phosphorylated by an upstream kinase, is active when released from a complex with the regulatory subunit upon the binding of cAMP (see [[http://proteopedia.org/wiki/index.php/CAMP_Dependent_Protein_Kinase%2C_Catalytic_Subunit]]. Calcium-dependent protein kinase has calcium-binding domain that blocks the active site in the absence of calcium<ref>PMID:20436473</ref>. Upon binding calcium the latter domain undergoes a dramatic conformational change and it moves to a binding site that is on opposite side of the kinase, thus unblocking the catalytic cleft.

=References=

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 . These scenes show the alignments of structures critical for activity. The yellow Cα-trace is the DFG-activation loop sequence, the blue trace is the catalytic loop, and the orchid trace is the C-helix (subdomain III). In ball and stick are residues critical for catalytic activity: yellow is the D in DFG, which binds Mg<sup>2+</sup>; blue is the D in the YRDKLPEN, which is the catalytic base;  cyan is the invariant K of subdomain II, which binds the phosphates of ATP; and orchid is the invariant E of subdomain III. The positions needed for catalysis can be seen in the closed, active kinase (left). The two D's and K are pointing toward ANP, and the E is bound to the K. The latter pulls the C-helix into position. In the open structure (middle) the elements of the large lobe are in place but the K of the small lobe is far away from the ANP binding site. Upon ATP binding the K interacts with the phosphates and the two lobes close. The view of the inactive structure (right) is oriented so that the backbones of the catalytic loop (blue) and ends of the activation loop (yellow) are positioned like those in the other two structures. The other residues of the activation loop are not shown because they were not resolved in the crystal structure because of their flexibility. The side chain of the D in the catalytic loop (blue ball and stick)points away from the ATP binding pocket, and the C-helix is rotated upward. The assembly of these elements depends on the phosphorylation of threonine 197 in the activation loop. The phosphate of the residue forms five critical bonds that align the active site structures<ref>PMID:22334660</ref>.
+===Regulation of Protein Kinase Activity===
+There are a variety of ways that the activity of protein kinases are regulated. Here are a few examples. Some are regulated via phosphorylation of residue(s) in the activation loop by either an upstream protein kinase (such as [[mitogen-activated protein kinase]] phosphorylation by MAPKK) or by autophosphosphorylation stimulated by the binding of a ligand (such as the insulin receptor kinase<ref>PMID:7997262</ref>). Others are activated by binding with other proteins, which brings the kinase into the active conformation. The PKA C subunit, having been constitutively phosphorylated by an upstream kinase, is active when released from a complex with the regulatory subunit upon the binding of cAMP (see [[http://proteopedia.org/wiki/index.php/CAMP_Dependent_Protein_Kinase%2C_Catalytic_Subunit]]. Calcium-dependent protein kinase has calcium-binding domain that blocks the active site in the absence of calcium<ref>PMID:20436473</ref>. Upon binding calcium the latter domain undergoes a dramatic conformational change and it moves to a binding site that is on opposite side of the kinase, thus unblocking the catalytic cleft.
 =References=
 <references/>