Sandbox Reserved 957: Difference between revisions

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You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

PDE5, phosphodiesterase 5 (EC 3.1.4.35), is an abundant protein in cell of airway and visceral smooth muscle and vascular cell. It can be found in epithelial cell and in Purkinje cell of the cerebella [1] and platelets and Corpus Cavernosum. In particular, it is implied in the NO pathway of penile erection and so in the Erectile Dysfunction (ED) [22].

PDE5, phosphodiesterase 5 (EC 3.1.4.35), is an abundant protein in cell of airway and visceral smooth muscle and vascular cell. It can be found in epithelial cell and in Purkinje cell of the cerebella [1] and platelets and Corpus Cavernosum. In particular, it is implied in the NO pathway of penile erection and so in the Erectile Dysfunction (ED) [22].<br \>

There are 11 families of PDE (from 1 to 9), there is 21 genes for PDE which code 60 different PDE. For the PDE5A, the only PDE5 subcategory, there are 4 isoforms but their catalytic domain is the same [24].

There are 11 families of PDE (from 1 to 9), there is 21 genes for PDE which code 60 different PDE. For the PDE5A, the only PDE5 subcategory, there are 4 isoforms but their catalytic domain is the same [24].<br \>

The catalytic reaction is the hydrolysis of guanosine cyclic monophosphate into linear guanosine monophosphate. This cGMP-specific enzyme have 3 domains (from N terminal to C terminal) : GAF A, GAF B and a conserved catalytic domain regard to other PDEs of the family. Only cGMP can bind GAF A or GAF B and it stimulates the hydrolysis.

The catalytic reaction is the hydrolysis of guanosine cyclic monophosphate into linear guanosine monophosphate. This cGMP-specific enzyme have 3 domains (from N terminal to C terminal) : GAF A, GAF B and a conserved catalytic domain regard to other PDEs of the family. Only cGMP can bind GAF A or GAF B and it stimulates the hydrolysis.<br \>

We study here the PDE5A catalytic fragment formed of amino acid residues from the 535th to the 860th [23]. In the inhibition, we talk about the Sildenafil mostly, because it's the most known (active ingredient in the Viagra®).

== Structure of catalytic site ==

The only catalytic fragment is effective, so the regulations sites and the dimerization to a trimeric enzyme are useless for the catalytic activity. Moreover, this catalytic moiety has the same activity that the wild-type enzyme, so maybe the enzyme is monomeric in the cell [24].

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]./n

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].

The catalytic domain has 3 helical subdomains [24]:/n

The catalytic domain has 3 helical subdomains [24]:

- A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 310-helixes (2,4, and 7), from the 537th to the 678th residues./n

- A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 310-helixes (2,4, and 7), from the 537th to the 678th residues.

- A linker domain: two antiparallels α9 and α10 helixes, and between a disordered region, from the 679th to the 725th residues.

- 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), from the 726th to the 860th residues.

Sandbox Reserved 957: Difference between revisions

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@@ Line 5: / Line 5: @@
 You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-PDE5, phosphodiesterase 5 (EC 3.1.4.35), is an abundant protein in cell of airway and visceral smooth muscle and vascular cell. It can be found in epithelial cell and in Purkinje cell of the cerebella [1] and platelets and Corpus Cavernosum. In particular, it is implied in the NO pathway of penile erection and so in the Erectile Dysfunction (ED) [22].
+PDE5, phosphodiesterase 5 (EC 3.1.4.35), is an abundant protein in cell of airway and visceral smooth muscle and vascular cell. It can be found in epithelial cell and in Purkinje cell of the cerebella [1] and platelets and Corpus Cavernosum. In particular, it is implied in the NO pathway of penile erection and so in the Erectile Dysfunction (ED) [22].<br \>
-There are 11 families of PDE (from 1 to 9), there is 21 genes for PDE which code 60 different PDE. For the PDE5A, the only PDE5 subcategory, there are 4 isoforms but their catalytic domain is the same [24].
+There are 11 families of PDE (from 1 to 9), there is 21 genes for PDE which code 60 different PDE. For the PDE5A, the only PDE5 subcategory, there are 4 isoforms but their catalytic domain is the same [24].<br \>
-The catalytic reaction is the hydrolysis of guanosine cyclic monophosphate into linear guanosine monophosphate. This cGMP-specific enzyme have 3 domains (from N terminal to C terminal) : GAF A, GAF B and a conserved catalytic domain regard to other PDEs of the family. Only cGMP can bind GAF A or GAF B and it stimulates the hydrolysis.
+The catalytic reaction is the hydrolysis of guanosine cyclic monophosphate into linear guanosine monophosphate. This cGMP-specific enzyme have 3 domains (from N terminal to C terminal) : GAF A, GAF B and a conserved catalytic domain regard to other PDEs of the family. Only cGMP can bind GAF A or GAF B and it stimulates the hydrolysis.<br \>
 We study here the PDE5A catalytic fragment formed of amino acid residues from the 535th to the 860th [23]. In the inhibition, we talk about the Sildenafil mostly, because it's the most known (active ingredient in the Viagra®).
 == Structure of catalytic site ==
 The only catalytic fragment is effective, so the regulations sites and the dimerization to a trimeric enzyme are useless for the catalytic activity. Moreover, this catalytic moiety has the same activity that the wild-type enzyme, so maybe the enzyme is monomeric in the cell [24].
-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]./n
+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].
-The catalytic domain has 3 helical subdomains [24]:/n
+The catalytic domain has 3 helical subdomains [24]:
-- A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 310-helixes (2,4, and 7), from the 537th to the 678th residues./n
+- A N-terminal cyclin-fold region with eight helixes [26]: 5 α-helixes (1, 3, 5, 6 and 8) and 3 310-helixes (2,4, and 7), from the 537th to the 678th residues.
 - A linker domain: two antiparallels α9 and α10 helixes, and between a disordered region, from the 679th to the 725th residues.
 - 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), from the 726th to the 860th residues.