Nitric Oxide Synthase: Difference between revisions

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The <scene name='Sandbox_5/Nos_oxygenase_med_cofaktore/3'>oxygenase domain</scene>(PDB:2G6H) contains the active site of the enzyme. The active site binds the substrate <scene name='Nitric_oxide_synthase/Nos_oxygenase_arg/3'>L-Arginine</scene>~~(PDB:2G6H)~~ ([http://en.wikipedia.org/wiki/Arginine Arginine]) which is converted into citruline and NO (explained in details below). The domain has three cofactors bound:

The <scene name='Sandbox_5/Nos_oxygenase_med_cofaktore/3'>oxygenase domain</scene>(PDB:2G6H) contains the active site of the enzyme. The active site binds the substrate <scene name='Nitric_oxide_synthase/Nos_oxygenase_arg/3'>L-Arginine</scene>([http://en.wikipedia.org/wiki/Arginine Arginine]) which is converted into citruline and NO (explained in details below). The domain has three cofactors bound:

<scene name='Nitric_oxide_synthase/Nos_oxygenase_bh4/1'>H4B</scene> ([http://en.wikipedia.org/wiki/BH4 (6R).5,6,7,8-Tetrahydrobiopterin]~~)(PDB:2G6H~~)

<scene name='Nitric_oxide_synthase/Nos_oxygenase_bh4/1'>H4B</scene> ([http://en.wikipedia.org/wiki/BH4 (6R).5,6,7,8-Tetrahydrobiopterin])

<scene name='Nitric_oxide_synthase/Nos_oxygenase_heme/1'>Heme</scene> ([http://en.wikipedia.org/wiki/Heme Heme]~~)(PDB:2G6H~~)

<scene name='Nitric_oxide_synthase/Nos_oxygenase_heme/1'>Heme</scene> ([http://en.wikipedia.org/wiki/Heme Heme])

<scene name='Nitric_oxide_synthase/Nos_oxygenase_zinc/4'>Zinc ion</scene>~~(PDB:2G6H)~~

==== General Structure ====

=== General Structure ===

The oxygenase domain can be divided into three subdomains. Firstly, the substrate-binding subdomain, which is crescent in shape, binds the substrate in an interior pocket of the crescent. The Heme group is located between the tips of the crescent shape, thus closing the pocket in which the substrate is located. Secondly the H4B binding subdomain serves as a cap for the cavity created by the substrate binding domains crescent shape. Thirdly there is a subdomain with two helical bundles making up a hydrophobic core, however this subdomain is not thought to take part in the catalytic activity of the enzyme.

==== Substrate binding ====

=== Substrate binding ===

The active site is highly conserved in the different NOS species. Thus it is possible to discuss substrate binding i general terms. The NOS enzyme binds its substrate (L-arginine) in the distal pocket by hydrogen bindings both to the guanidino[http://en.wikipedia.org/wiki/Guanidino] end and the amino acid end. <scene name='Nitric_oxide_synthase/Substratebinding_test/1'>Substrate in the catalytic site</scene>~~(PDB:3NOS)~~ is shown in green with the heme and H4B shown. NOS binds its substrate by coordinating CO(or O2) to the heme at the site occupied by oxygen<ref>PMID:9376373 </ref>(it is the opposite site of the Cys coordination to heme - look in the 'heme' section). The binding of substrate leads to a 2-step transformation first to N-hydroxy-L-arginine (the tightly bound intermediate) and then NO and L-Citrulline. The product NO can then either diffuse out of the <scene name='Nitric_oxide_synthase/Substratebinding_distal_pocket/1'>cavity</scene>~~(PDB:3NOS)~~ or bind to the heme and function in NO auto-inhibition though this inhibition is diverse throughout the 3 isoforms<ref>PMID:15598509</ref>.

The active site is highly conserved in the different NOS species. Thus it is possible to discuss substrate binding i general terms. The NOS enzyme binds its substrate (L-arginine) in the distal pocket by hydrogen bindings both to the guanidino[http://en.wikipedia.org/wiki/Guanidino] end and the amino acid end. <scene name='Nitric_oxide_synthase/Substratebinding_test/1'>Substrate in the catalytic site</scene> is shown in green with the heme and H4B shown. NOS binds its substrate by coordinating CO(or O2) to the heme at the site occupied by oxygen<ref>PMID:9376373 </ref>(it is the opposite site of the Cys coordination to heme - look in the 'heme' section). The binding of substrate leads to a 2-step transformation first to N-hydroxy-L-arginine (the tightly bound intermediate) and then NO and L-Citrulline. The product NO can then either diffuse out of the <scene name='Nitric_oxide_synthase/Substratebinding_distal_pocket/1'>cavity</scene> or bind to the heme and function in NO auto-inhibition though this inhibition is diverse throughout the 3 isoforms<ref>PMID:15598509</ref>.

PDB structures used in the section above: [[http://www.proteopedia.org/wiki/index.php/3nos 3NOS]], [[http://www.proteopedia.org/wiki/index.php/2g6h 2G6H]]

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Nitric Oxide Synthase: Difference between revisions

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@@ Line 21: / Line 21: @@
 <applet load='2g6h' size='300' color='white' frame='true' align='right' caption='Oxygenase domain' />
-The <scene name='Sandbox_5/Nos_oxygenase_med_cofaktore/3'>oxygenase domain</scene>(PDB:2G6H) contains the active site of the enzyme. The active site binds the substrate <scene name='Nitric_oxide_synthase/Nos_oxygenase_arg/3'>L-Arginine</scene>(PDB:2G6H) ([http://en.wikipedia.org/wiki/Arginine Arginine]) which is converted into citruline and NO (explained in details below). The domain has three cofactors bound:
+The <scene name='Sandbox_5/Nos_oxygenase_med_cofaktore/3'>oxygenase domain</scene>(PDB:2G6H) contains the active site of the enzyme. The active site binds the substrate <scene name='Nitric_oxide_synthase/Nos_oxygenase_arg/3'>L-Arginine</scene>([http://en.wikipedia.org/wiki/Arginine Arginine]) which is converted into citruline and NO (explained in details below). The domain has three cofactors bound:
-<scene name='Nitric_oxide_synthase/Nos_oxygenase_bh4/1'>H4B</scene> ([http://en.wikipedia.org/wiki/BH4 (6R).5,6,7,8-Tetrahydrobiopterin])(PDB:2G6H)
+<scene name='Nitric_oxide_synthase/Nos_oxygenase_bh4/1'>H4B</scene> ([http://en.wikipedia.org/wiki/BH4 (6R).5,6,7,8-Tetrahydrobiopterin])
-<scene name='Nitric_oxide_synthase/Nos_oxygenase_heme/1'>Heme</scene> ([http://en.wikipedia.org/wiki/Heme Heme])(PDB:2G6H)
+<scene name='Nitric_oxide_synthase/Nos_oxygenase_heme/1'>Heme</scene> ([http://en.wikipedia.org/wiki/Heme Heme])
-<scene name='Nitric_oxide_synthase/Nos_oxygenase_zinc/4'>Zinc ion</scene>(PDB:2G6H)
+<scene name='Nitric_oxide_synthase/Nos_oxygenase_zinc/4'>Zinc ion</scene>
-==== General Structure ====
+=== General Structure ===
 The oxygenase domain can be divided into three subdomains. Firstly, the substrate-binding subdomain, which is crescent in shape, binds the substrate in an interior pocket of the crescent. The Heme group is located between the tips of the crescent shape, thus closing the pocket in which the substrate is located. Secondly the H<sub>4</sub>B binding subdomain serves as a cap for the cavity created by the substrate binding domains crescent shape. Thirdly there is a subdomain with two helical bundles making up a hydrophobic core, however this subdomain is not thought to take part in the catalytic activity of the enzyme.
-==== Substrate binding ====
+=== Substrate binding ===
-The active site is highly conserved in the different NOS species. Thus it is possible to discuss substrate binding i general terms. The NOS enzyme binds its substrate (L-arginine) in the distal pocket by hydrogen bindings both to the guanidino[http://en.wikipedia.org/wiki/Guanidino] end and the amino acid end. <scene name='Nitric_oxide_synthase/Substratebinding_test/1'>Substrate in the catalytic site</scene>(PDB:3NOS) is shown in green with the heme and H<sub>4</sub>B shown. NOS binds its substrate by coordinating CO(or O<sub>2</sub>) to the heme at the site occupied by oxygen<ref>PMID:9376373 </ref>(it is the opposite site of the Cys coordination to heme - look in the 'heme' section). The binding of substrate leads to a 2-step transformation first to N-hydroxy-L-arginine (the tightly bound intermediate) and then NO and L-Citrulline. The product NO can then either diffuse out of the <scene name='Nitric_oxide_synthase/Substratebinding_distal_pocket/1'>cavity</scene>(PDB:3NOS) or bind to the heme and function in NO auto-inhibition though this inhibition is diverse throughout the 3 isoforms<ref>PMID:15598509</ref>.
+The active site is highly conserved in the different NOS species. Thus it is possible to discuss substrate binding i general terms. The NOS enzyme binds its substrate (L-arginine) in the distal pocket by hydrogen bindings both to the guanidino[http://en.wikipedia.org/wiki/Guanidino] end and the amino acid end. <scene name='Nitric_oxide_synthase/Substratebinding_test/1'>Substrate in the catalytic site</scene> is shown in green with the heme and H<sub>4</sub>B shown. NOS binds its substrate by coordinating CO(or O<sub>2</sub>) to the heme at the site occupied by oxygen<ref>PMID:9376373 </ref>(it is the opposite site of the Cys coordination to heme - look in the 'heme' section). The binding of substrate leads to a 2-step transformation first to N-hydroxy-L-arginine (the tightly bound intermediate) and then NO and L-Citrulline. The product NO can then either diffuse out of the <scene name='Nitric_oxide_synthase/Substratebinding_distal_pocket/1'>cavity</scene> or bind to the heme and function in NO auto-inhibition though this inhibition is diverse throughout the 3 isoforms<ref>PMID:15598509</ref>.
+PDB structures used in the section above: [[http://www.proteopedia.org/wiki/index.php/3nos 3NOS]], [[http://www.proteopedia.org/wiki/index.php/2g6h 2G6H]]
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