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. Its structural importense is also 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. The substrate is H-bonded to the 4-keto group of pterin, and to one of the heme propionate groups, that has two carboxylate oxygens in use for H-bonds. These oxygens are further H-bonded to the 4-keto group of pterin, through water, and directly to N(3) and NH<sub>2</sub> on C (2). The big picture of all the H-bonds can be seen on figure (???)-lav figur i chemdraw inspireret af figuren s. 943Raman))) | The H<sub>4</sub>B is bound by hydrogen-bonds to several of the molekules surrounding it, including the substrate L-Arg. The substrate is H-bonded to the 4-keto group of pterin, and to one of the heme propionate groups, that has two carboxylate oxygens in use for H-bonds. These oxygens are further H-bonded to the 4-keto group of pterin, through water, and directly to N(3) and NH<sub>2</sub> on C (2). The big picture of all the H-bonds can be seen on figure (???)-lav figur i chemdraw inspireret af figuren s. 943Raman))) | ||
But H<sub>4</sub>B is not 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. (indsæt fig.3 i artiklen) As shown in the reaction (fig.3) the second electron, that H<sub>4</sub>B donates helps the Fe<sup>II</sup>O<sub>2</sub> intermadiate to be reduced in to oxidants that can react with Arg and N-hydroxy-L-arginine (NOHA) <ref>PMID: 12237227 </ref> If H<sub>4</sub>B was not present the Fe<sup>II</sup>O<sub>2</sub> intermediate would decay to superoxide and ferric enzyme, because the reductase domain is slower to deliver an electron, than the proces of decay is to happen. But H<sub>4</sub>B is faster than both of these processes. <ref>PMID: 12237227 </ref> | |||
===Heme=== | ===Heme=== | ||