User:Alice Harmon/Sandbox 1: Difference between revisions
Alice Harmon (talk | contribs) No edit summary |
Alice Harmon (talk | contribs) |
||
Line 53: | Line 53: | ||
The kinase structure used in the above tour is that of the active conformation of PKA. Following is a comparison of this active conformation, with its particular arrangement of structural elements, to the inactive conformation. While active conformations of protein kinases are very similar, there is great variation in the inactive conformations of protein kinases, but all involve misalignment of one or more of the structures, subdomain III (C-helix in PKA) and the catalytic, magnesium binding, and activation loops<ref name = "TaylorTIBS"/>. | The kinase structure used in the above tour is that of the active conformation of PKA. Following is a comparison of this active conformation, with its particular arrangement of structural elements, to the inactive conformation. While active conformations of protein kinases are very similar, there is great variation in the inactive conformations of protein kinases, but all involve misalignment of one or more of the structures, subdomain III (C-helix in PKA) and the catalytic, magnesium binding, and activation loops<ref name = "TaylorTIBS"/>. | ||
To get an idea of the structural differences in active and inactive kinase domains, here is the structure of inactive apo-PKA ([[1J3H]]on the left, and on the right is PKA in complex with ANP and PKI ([[1atp]], the same structure used above). The catalytic domains are shown in spacefill, with the large lobe in silver and the small lobe in blue. To aid viewing, The N and C terminal sequences are in cartoon. Stop the rotation and use your mouse to get a good look at the catalytic cleft, which in 1ATP is closed around ANP. Two sets of residues are shown in yellow and red, respectively, to show the degree to which the cleft opens, and the two lobes twist with respect to each other. The yellow residues are Gly52 from the GxGxxG motif and Thr 201 in the activation loop. The red residues are His 87 in subdomain III (the C helix) and phosphorthreonine 197 in the activation loop. Note the difference in distance and alignment of these pairs of residues. In the closed, active conformation His 87 and phosphoThr 197 have an ionic interaction, whereas in the openconformation they are too far away from each other to interact. | |||
Line 59: | Line 61: | ||
<Structure load='1J3H' size='350' frame='true' align='right' caption='1j3h - apo-PKA' scene='55/555705/Apopka/2' /> | <Structure load='1J3H' size='350' frame='true' align='right' caption='1j3h - apo-PKA' scene='55/555705/Apopka/2' /> | ||
<scene name='55/555705/Twistedlobes/2'>Open, inactive conformation</scene> | <scene name='55/555705/Twistedlobes/2'>Open, inactive conformation</scene> | ||
=References= | =References= | ||
<references/> | <references/> |