User:Alice Harmon/Sandbox 1: Difference between revisions
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The kinase structure used in the above tour is that of the active conformation of PKA. 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. 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 that occur during a catalytic cycle and | To get an idea of the structural differences that occur during a catalytic cycle and in active and inactive enzymes, use the links below to compare inactive, unphosphorylated PKA [[4dfy]] (activation loop threonine is not phosphorylated), and active PKA in complex with ANP and PKI [[1atp]] (the same structure used above), active apo PKA [[1j3h]], shown in the left, middle, and right frames, respectively. 4dfy shows the structure of an inactive form of PKA, in which the internal structure is disorganized due to the lack of phosphorylation of threonine 197 in the activation loop. Phosphorylation is required for formation of hydrogen bonds that are critical for alignment of structures to form the active site. 1j3h and 1atp show the open and closed structures assumed by PKA during the catalytic cycle. Note that some residues in 1j3h and 4dfy are not depicted in the models, because they are disordered and not resolved in the structures. | ||
< | Click on all three links with same number to compare the indicated features. Legends for each set of scenes are below. To reset the structures, reload the page. | ||
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| <applet load='4DFY' size='300' frame='true' align='right' caption='4dfy - apo unphosphorylated PKA, inactive' scene='55/555705/Unphospka/3' /><Br>'''4dfy'''<Br><scene name='55/555705/Unphospka_spacefill/2'>1. Inactive conformation</scene><br><scene name='55/555705/Unphospka_spines/1'>2. Disassembled spines</scene><br><scene name='55/555705/Unphoscritical/2'>3. Critical structures</scene> | |||
| <applet load='1J3H' size='300' frame='true' align='right' caption='1j3h - apo PKA, open conformation' scene='55/555705/Apopka/2' /><Br>'''1j3h''': <Br><scene name='55/555705/Twistedlobes/2'>1. Open conformation</scene><br><scene name='55/555705/Apo_spines/1'>2. Assembled, open spines</scene><br><scene name='55/555705/Apo_critical/2'>3. Critical structures</scene> | |||
| <applet load='1atp' size='300' frame='true' align='right' caption='1atp - PKA with ANP and PKI; closed and active' scene='55/555705/Pkaall/1' /><Br>'''1atp:''' <Br><scene name='55/555705/Closedlobes/4'>1. Closed, active conformation</scene><br><scene name='55/555705/Both_spines/2'>2. Assembled, closed spines</scene><Br><scene name='55/555705/Pkacritical/2'>3. Critical structures</scene> | |||
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