Nitric Oxide Synthase: Difference between revisions
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[[image:H4b_hydrogenbindinger2.png|thumb|left|Hydrogenbondings in H<sub>4</sub>B binding site]] | [[image:H4b_hydrogenbindinger2.png|thumb|left|Hydrogenbondings in H<sub>4</sub>B binding site]] | ||
The H<sub>4</sub>B is bound by hydrogen-bonds to several of the molecules 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 ( the heme propionate group 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)<ref name="Raman"/>. The overall picture of all the H-bonds can be seen by clicking on the figure on the left. [[image:mette.png|thumb|right|model for NOS oxygen activation]] | The H<sub>4</sub>B is bound by hydrogen-bonds to several of the molecules 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 ( the heme propionate group 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)<ref name="Raman"/>. The overall picture of all the H-bonds can be seen by clicking on the figure on the left. [[image:mette.png|thumb|right|model for NOS oxygen activation]] | ||
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. Thus, H<sub>4</sub>B is a kinetically prefered electron donor. As shown in the reaction (bottom right, click for enlargement) the second electron, that H<sub>4</sub>B donates, helps the Fe<sup>II</sup>O<sub>2</sub> intermediate to be reduced to oxidants that are able to react with Arg and N-hydroxy-L-arginine (NOHA) <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 name="heme">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. Thus, H<sub>4</sub>B is a kinetically prefered electron donor. As shown in the reaction (bottom right, click for enlargement) the second electron, that H<sub>4</sub>B donates, helps the Fe<sup>II</sup>O<sub>2</sub> intermediate to be reduced to oxidants that are able to react with Arg and N-hydroxy-L-arginine (NOHA) <ref name="heme"/> 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 due to the reductase domain being slower to deliver an electron than the proces of decay is to happen. H<sub>4</sub>B is faster than both of these processes<ref name="heme"/>. | ||
