Nitric Oxide Synthase: Difference between revisions
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[[image:bh4.png|left|frame|Structure of tetrahydrobiopterin]] | [[image:bh4.png|left|frame|Structure of tetrahydrobiopterin]] | ||
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<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. | <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. | ||
But H<sub>4</sub>B is only a structurel cofactor, it also plays a very important role in NO synthesis, donating an electron to the heme.<ref>PMID: 12237227 </ref> H<sub>4</sub>B can deliver an electron to the heme much faster than the reductase domain can, therefor H<sub>4</sub>B is used by NOS in the Arg hydroxylation, activating O<sub>2</sub> by providing the second electron. So H<sub>4</sub>B is a kinetically prefered electron donor. | |||
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> | ||