Nitric Oxide Synthase: Difference between revisions
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===H<sub>4</sub>B=== | ===H<sub>4</sub>B=== | ||
[[image:bh4.png|right|frame|Structure of tetrahydrobiopterin]] | [[image:bh4.png|right|frame|Structure of tetrahydrobiopterin]] | ||
<applet load='2g6h' size='300' frame='true' align='right' caption='Insert caption here' /> | |||
<scene name='Sandbox_5/Nos_oxygenase_bh4/11'>H4B</scene> is a cofactor. NOS contains two molecules of <scene name='Sandbox_5/Begge_h4b/1'>H4B</scene>, one in each monomer. The active center forms a kind of tunnel, because of the dimeric structure. This gives H<sub>4</sub>B the opportunity to play a big role in the control of subunit interactions and active-center formation. H<sub>4</sub>B therefor is more of a structurel cofactor, in that it keeps the dimer stabilized by integration in to the hydrophobic parts of the dimer. Here it helps substrate interactions by lining the active-center channel and hydrogen bonding to the heme propionate amd to alfa7 which is two elements involved in L-Arg binding. So H<sub>4</sub>B is not the molecule that hydroxylates the substrate (L-Arg) nor activating the hemebound oxygen. | <scene name='Sandbox_5/Nos_oxygenase_bh4/11'>H4B</scene> is a cofactor. NOS contains two molecules of <scene name='Sandbox_5/Begge_h4b/1'>H4B</scene>, one in each monomer. The active center forms a kind of tunnel, because of the dimeric structure. This gives H<sub>4</sub>B the opportunity to play a big role in the control of subunit interactions and active-center formation. H<sub>4</sub>B therefor is more of a structurel cofactor, in that it keeps the dimer stabilized by integration in to the hydrophobic parts of the dimer. Here it helps substrate interactions by lining the active-center channel and hydrogen bonding to the heme propionate amd to alfa7 which is two elements involved in L-Arg binding. So H<sub>4</sub>B is not the molecule that hydroxylates the substrate (L-Arg) nor activating the hemebound oxygen. | ||
Pterin induces some changes in the heme invironment, including ordering of the active-center channel, increased sequestration (sequestration (om proces) the action of forming a chelate or other stable compound with an ion or atom or molecule so that it is no longer available for reactions) of the heme ligand Cys194, and extension of the negative hemeA propionate away from the distal heme pocket may account for the 50mV increase in heme redox potential and low-high spin shift of the ferric heme iron in the presence og H<sub>4</sub>B. It also may increase the oxygen activation, because of the pterin-induced 70-fold increase in autoxidation of the ferrous heme-dioxy complex.<ref>PMID: 9516116 </ref> | Pterin induces some changes in the heme invironment, including ordering of the active-center channel, increased sequestration (sequestration (om proces) the action of forming a chelate or other stable compound with an ion or atom or molecule so that it is no longer available for reactions) of the heme ligand Cys194, and extension of the negative hemeA propionate away from the distal heme pocket may account for the 50mV increase in heme redox potential and low-high spin shift of the ferric heme iron in the presence og H<sub>4</sub>B. It also may increase the oxygen activation, because of the pterin-induced 70-fold increase in autoxidation of the ferrous heme-dioxy complex.<ref>PMID: 9516116 </ref> | ||
It is also known that H<sub>4</sub>B works as a elctron donor to reduce a oxyferrous complex (HVAD ER DETTE) from Fe (III) to Fe(II), but as stated above, it does not reduce the ferric heme.<ref>PMID: 17014963 </ref> | It is also known that H<sub>4</sub>B works as a elctron donor to reduce a oxyferrous complex (HVAD ER DETTE) from Fe (III) to Fe(II), but as stated above, it does not reduce the ferric heme.<ref>PMID: 17014963 </ref> | ||
It is still not quite certain what the role of H<sub>4</sub>B is. But its structural importense is reconned to play a role in dimer formation, and major conformational changes leading to the formation af the active site channelform.<ref>PMID:9875848</ref>. | |||
The H<sub>4</sub>B is bound by hydrogen-bonds to several of the molekules surrounding it, including the substrate L-Arg. | |||
===Heme=== | ===Heme=== | ||
