The Nitric Oxide-Releasing Heme

The Nitric Oxide-Releasing Heme Proteins from the Saliva of the Blood-Sucking Insect Rhodnius prolixus F. Ann Walker and William R. Montfort... 

THE NITRIC OXIDE-RELEASING HEME PROTEINS FROM THE SALIVA OF THE BLOOD-SUCKING INSECT Rhodnius prolixus... 

F. A. Walker and W. R. Montfort, The Nitric Oxide-Releasing Heme Proteins from the Saliva of the Blood-Sucking Insect Rhodniusprolixus, in Advances in Inorganic Chemistry , eds. A. G. Mauk and A. G. Sykes, Academic Press, San Diego, CA, 2001, Vol. 51, Chap. 5, p. 295. 

In summary, there is still much to understand about the nitrite reduction reaction. The crystal structures have shown how nitrite can bind to the di heme iron and protons can be provided to one of its oxygen atoms from two histidine residues. However, as yet no rapid reaction study has detected the release of product nitric oxide rather than the formation of the inhibitory dead-end ferrous di heme-NO complex. It is also not clear why the rate of interheme electron transfer is so slow over 11 A when nitrite or nitric oxide is the ligand to the d heme. 

Nitrosothiols should not bind directly to the heme of guanylate cyclase, but rather to activate guanylate cyclase by releasing nitric oxide. The simple cleavage of nitrosothiols into nitric oxide and a thiol radical is energetically expensive, so the activation may involve an oxidation with a second thiol group. 

Release of nitric oxide from the d heme can happen in more than one way. Delocalization is not continuous in the d heme and, as a consequence, the four nitrogen ligands surrounding the iron in the heme plane are not equivalent. Tyr25 or another ligand that can bond temporarily between the histidines may facilitate NO release, influenced by their protonation (or lack thereof). 

Nitrophorins (NP), nitric oxide (NO) transport proteins from the saliva of the bloodsucking insect Rhodniusprolixus that uses a ferric (Fe +) heme to deliver NO to the victims. Nitrophorins act as vasodilators and anti-platelet agents. At the tissue of the victim, the released NO molecule in the vicinity of the bite causes host signaling pathways that lead to vasodilation and reduced platelet aggregation. From crystal structure analysis of NPl and NP4 it follows that the nitrophorins have a unique hemopro-tein structure and are completely unlike the globins [J. M. C. Ribeiro et al.. Science 1993, 260, 539 J. F. Andersen et al.. Structure 1998, 6, 1315 E. M. Maes et al.. Biochemistry 2005, 44, 12690]. 

A second proteinaceous fraction, nitric oxide reductase, containing a bound c-type cytochrome converts nitric oxide to nitrous oxide (Matsubara and Iwasaki, 1971 Payne et al., 1971 Cox and Payne, 1973). The enzyme is soluble in Pseudomonas perfectomarinus (Cox and Payne, 1973), but is particulate in Alcaligenes faecalis and Pseudomonas denitrificans (Matsubara and Iwasaki, 1971 Miyata et al., 1969). Epr studies indicate no metal involvement but the formation of a different heme nitric oxide complex during release of nitrous oxide (Payne et al., 1971). The physiological electron donors are not known. FADHa, reduced phenazine methosulphate, and reduced viologen dyes have been found to be effective (Thauer et al., 1977). 

---