Nitric Oxide Synthase: Difference between revisions

<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 is a part of the cavity already described. This cavity can be visualized as a <scene name='Nitric_oxide_synthase/Substratebinding_distal_pocket/2'>tunnel</scene>. Here H₄B helps substrate interactions by lining the active-center tunnel and hydrogen bonding to the heme propionate amd to alfa7. Amd and alfa7 are two elements involved in L-Arg binding. This gives H₄B the opportunity to play an important role in the control of subunit interactions and active-center formation. H₄B is therefore more or less a structural cofactor and has a stabilizing effect. Its structural importance is further reconned to play a role in dimer formation (dimerization requires bound zinc ion along with H₄B), and major conformational changes leading to the formation of the active site channelform<ref>PMID:9875848</ref>.

The H₄B 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 NH₂ on C (2)<ref>PMID:9875848</ref>. 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 H₄B 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> H₄B can deliver an electron to the heme much faster than the reductase domain can, therefor H₄B is used by NOS in the Arg hydroxylation, activating O₂ by providing the second electron. Thus, H₄B is a kinetically prefered electron donor. As shown in the reaction (bottom right, click for enlargement) the second electron, that H₄B donates, helps the Fe^IIO₂ intermediate to be reduced to oxidants that are able to react with Arg and N-hydroxy-L-arginine (NOHA) <ref>PMID: 12237227 </ref> If H₄B was not present the Fe^IIO₂ 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. H₄B is faster than both of these processes. <ref>PMID: 12237227 </ref>