Nitric Oxide Synthase: Difference between revisions
| Line 54: | Line 54: | ||
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> | 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. [[image:mette.png|left|frame|model for NOS oxygen activation]](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=== | ||