Sandbox Reserved 957: Difference between revisions
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Catalytic domain is conserved for the PDE family, between 20% and 40%, and the variant reactions of the PDE inhibitors on the different PDEs may be caused by the more variant regulatory sites [25].<br \> | Catalytic domain is conserved for the PDE family, between 20% and 40%, and the variant reactions of the PDE inhibitors on the different PDEs may be caused by the more variant regulatory sites [25].<br \> | ||
The catalytic domain has 3 helical subdomains [24]:<br \> | The catalytic domain has 3 helical subdomains [24]:<br \> | ||
* A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 | * A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 3ind10-helixes (2,4, and 7),<scene name='60/604476/537_678/3'> from the 537th to the 678th residues</scene>.<br \> | ||
* A linker domain: two antiparallels α9 and α10 helixes, and between a disordered region,<scene name='60/604476/679-725/2'>from the 679th to the 725th residues</scene>.<br \> | * A linker domain: two antiparallels α9 and α10 helixes, and between a disordered region,<scene name='60/604476/679-725/2'>from the 679th to the 725th residues</scene>.<br \> | ||
* A C-terminal buddle pocket with eight helixes: 5 long α-helixes (11, 12, 14, 17 and 18) and 3 smaller helixes (13, 15 and 16),<scene name='60/604476/726-860/2'> from the 726th to the 860th residues</scene>.<br \> | * A C-terminal buddle pocket with eight helixes: 5 long α-helixes (11, 12, 14, 17 and 18) and 3 smaller helixes (13, 15 and 16),<scene name='60/604476/726-860/2'> from the 726th to the 860th residues</scene>.<br \> | ||
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For each inhibitor, <scene name='60/604476/H_loop/1'>H-loop</scene> take a different and originally (comparatively to other PDEs) tertiary structure (and there are also minor modifications of the N-loop (788-811) ):<br \> | For each inhibitor, <scene name='60/604476/H_loop/1'>H-loop</scene> take a different and originally (comparatively to other PDEs) tertiary structure (and there are also minor modifications of the N-loop (788-811) ):<br \> | ||
* For an unliganded PDE5, <scene name='60/604476/H_loop/1'>H-loop</scene> take a coil conformation. [21]<br \> | * For an unliganded PDE5, <scene name='60/604476/H_loop/1'>H-loop</scene> take a coil conformation. [21]<br \> | ||
* In case of Sildenafil binding, a turn and an | * In case of Sildenafil binding, a turn and an 3ind10<scene name='60/604476/3-10helix/1'> helix (from 672 to 675)</scene> appear, and residues from 668 to 676 are disordered. The all loop cover the active site (by migrate of 24 Å from unliganded PDE5 loop structure, so the active site become a closed pocket). [21]<br \> | ||
* H-loop is less important in the interactions for Sildenafil and Icarisid II than cGMP.<br \> | * H-loop is less important in the interactions for Sildenafil and Icarisid II than cGMP.<br \> | ||