Sandbox Reserved 957: Difference between revisions
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== Inhibition == | == Inhibition == | ||
In the treatment erection dysfunction, the inhibitors Sildenafil, Vardenafil and Tadalafil are used, like in the pulmonary hypertension<ref>[6]</ref>. Sildenafil may cure sleeping trouble after a intercontinental travel <ref>[11]</ref>, may help to recover neural liaisons after an injury (the motor function<ref>[12]</ref> and the sensory motor function<ref>[13]</ref>) and can be vascular effects.<br \> | In the treatment erection dysfunction, the inhibitors Sildenafil, Vardenafil and Tadalafil are used, like in the pulmonary hypertension<ref>[6]</ref>. Sildenafil may cure sleeping trouble after a intercontinental travel <ref>[11]</ref>, may help to recover neural liaisons after an injury (the motor function<ref>[12]</ref> and the sensory motor function<ref>[13]</ref>) and can be vascular effects.<br \> | ||
<gallery | <gallery>Image:Sildenafil.jpg|500px|Sildenafil Inhibitor, R1 in blue, R2 in green and R3 in red | ||
Image:Sildenafilspace.jpg|Sildenafil Inhibitor in the space in the enzyme</gallery> | Image:Sildenafilspace.jpg|500px|Sildenafil Inhibitor in the space in the enzyme</gallery> | ||
* PDE5 inhibitors might help physical condition in Duchene muscular dystrophy<ref>[14]</ref>, improve of cognitive function <ref>[9]</ref>and have antidepressant effect<ref>[10]</ref> , also they might have an artero<ref>[15]</ref> and endothelial cell protective effect<ref>[16]</ref> so they have cardiac protection effect<ref>[17]</ref> (controversial, cf. clinical trial “RELAX”), finally they slow tumer cell growth (Tadalafil-like)<ref>[18]</ref><br \> | * PDE5 inhibitors might help physical condition in Duchene muscular dystrophy<ref>[14]</ref>, improve of cognitive function <ref>[9]</ref>and have antidepressant effect<ref>[10]</ref> , also they might have an artero<ref>[15]</ref> and endothelial cell protective effect<ref>[16]</ref> so they have cardiac protection effect<ref>[17]</ref> (controversial, cf. clinical trial “RELAX”), finally they slow tumer cell growth (Tadalafil-like)<ref>[18]</ref><br \> | ||
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* 3 parts (R1: pyrazolopyrimidinone group; R2: ethoxyphenyl; R3: methylpiperazine)<br \> | * 3 parts (R1: pyrazolopyrimidinone group; R2: ethoxyphenyl; R3: methylpiperazine)<br \> | ||
* It is bound near Metallic ions but does not interact with them.<br \> | * It is bound near Metallic ions but does not interact with them.<br \> | ||
Binding amino acid for the Sildenafil:<br \> | Binding amino acid for the Sildenafil:<br \> | ||
* R1 group have contacts with <scene name='60/604476/R1-1/1'>Gln817</scene> (2 hydrogen bounds, so it increases Sildenafil affinity), <scene name='60/604476/R1-1/1'>Phe820</scene> (Sildenafil stacks against it), <scene name='60/604476/R1-1/1'>Try612</scene> (hydrogen bound so it increases Sildenafil affinity <ref>[24]</ref>), <scene name='60/604476/R1-1/1'>Leu765</scene> and <scene name='60/604476/R1-1/1'>Ala767</scene> <ref>[21]</ref>. And there is hydrophobic interactions between the pyrazol ring and residues <scene name='60/604476/R1-2/1'>Val782, Leu785, Tyr612 and Phe820</scene> <ref>[24]</ref>.<br \> | * R1 group have contacts with <scene name='60/604476/R1-1/1'>Gln817</scene> (2 hydrogen bounds, so it increases Sildenafil affinity), <scene name='60/604476/R1-1/1'>Phe820</scene> (Sildenafil stacks against it), <scene name='60/604476/R1-1/1'>Try612</scene> (hydrogen bound so it increases Sildenafil affinity <ref>[24]</ref>), <scene name='60/604476/R1-1/1'>Leu765</scene> and <scene name='60/604476/R1-1/1'>Ala767</scene> <ref>[21]</ref>. And there is hydrophobic interactions between the pyrazol ring and residues <scene name='60/604476/R1-2/1'>Val782, Leu785, Tyr612 and Phe820</scene> <ref>[24]</ref>.<br \> | ||
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</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
[1] Francis SH, Zoraghi R, Kotera J, Ke H, Bessay EP, Blount MA, Corbin JD. Phosphodiesterase-5: molecular characteristics relating to structure, function, and regulation. In: Cyclic Nucleotide Phosphodiesterases in Health and Disease, edited by Beavo JA, Houslay MD, Francis SH. Boca Raton, FL: CRC, 2006, p. 131–164.<br \> | [1] Francis SH, Zoraghi R, Kotera J, Ke H, Bessay EP, Blount MA, Corbin JD. Phosphodiesterase-5: molecular characteristics relating to structure, function, and regulation. In: Cyclic Nucleotide Phosphodiesterases in Health and Disease, edited by Beavo JA, Houslay MD, Francis SH. Boca Raton, FL: CRC, 2006, p. 131–164.<br \> | ||
Sekiguchi M, Hoshizaki H, Adachi H, Ohshima S, Taniguchi K, Kurabayashi M. Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting: a randomized comparison of ticlopidine and cilostazol. Circ J 68: 610–614, 2004. | Sekiguchi M, Hoshizaki H, Adachi H, Ohshima S, Taniguchi K, Kurabayashi M. Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting: a randomized comparison of ticlopidine and cilostazol. Circ J 68: 610–614, 2004. | ||
Sopory S, Kaur T, Visweswariah SS. The cGMP-binding, cGMPspecific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion. Cell Signal 16: 681–692, 2004.<br \> | Sopory S, Kaur T, Visweswariah SS. The cGMP-binding, cGMPspecific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion. Cell Signal 16: 681–692, 2004.<br \> | ||
Zhu B, Strada S, Stevens T. Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 289: L196–L206, 2005.<br \> | Zhu B, Strada S, Stevens T. Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 289: L196–L206, 2005.<br \> | ||
<references/> | |||
