Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.7.1.4 (nitrite reductase)
 1,847 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myoglobin, famous as an important intracellular oxygen binding hemeprotein, displays a variety of functions. The first pioneering review on myoglobin was published as early as 1939, in which Millikan concluded that "muscle hemoglobin" acts primarily as a short-term dioxygen store, tiding the muscle over from one contraction to the next. Since that time, myoglobin has become one of the most widely studied proteins in a variety of research fields ranging from chemistry to medicine. Recently it was discovered that in the heart myoglobin changes its function in dependence of oxygen tension, acting as an oxygen sensor. Under normoxic conditions myoglobin plays the role of a nitric oxide (NO(*)) scavenger, protecting the heart from the deleterious effects of excessive NO(*). During hypoxia however, myoglobin changes its role from an NO(*) scavenger to an NO(*) producer. Deoxygenated myoglobin reduces nitrite to bioactive NO(*). The produced NO(*) downregulates the cardiac energy status and reduces myocardial oxygen consumption, thus protecting the heart. Myoglobin also exhibits a nitrite reductase function under further pathophysiological conditions. During myocardial reperfusion after ischemia, myoglobin - via nitrite - regulates respiration and cellular viability. This leads to a dramatic reduction of myocardial infarct size and to an improvement of myocardial function. The reaction between myoglobin and nitrite thus seems to play an imminent role in the regulation of cardiac function in physiology and pathophysiology.
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PMID:A highlight of myoglobin diversity: the nitrite reductase activity during myocardial ischemia-reperfusion. 1983 57

Myoglobin is presumably the most studied protein in biology. Its functional properties as a dioxygen storage and facilitator of dioxygen transport are widely acknowledged. Experimental evidence also implicates an essential role for myoglobin in the heart in regulating nitric oxide homeostasis. Under normoxia, oxygenated myoglobin can scavenge excessive nitric oxide, while under hypoxia, deoxygenated myoglobin can reduce nitrite, an oxidative product of nitric oxide, to bioactive nitric oxide. Myoglobin-driven nitrite reduction can protect the heart from ischemia and reperfusion injury. While horse and mouse myoglobin have been previously described to reduce nitrite under these conditions, a comparable activity has not been detected in human myoglobin. We here show that human myoglobin is a fully functional nitrite reductase. To study the role of human myoglobin for nitric oxide homeostasis we used repeated photometric wavelength scans and chemiluminescence based experiments. The results revealed that oxygenated human myoglobin reacts with nitrite-derived nitric oxide to form ferric myoglobin and that deoxygenated human myoglobin acts as a nitrite reductase in vitro and in situ. Rates of both nitric oxide scavenging and nitrite reduction were significantly higher in human compared to horse myoglobin. These data extend the existing knowledge about the functional properties of human myoglobin and are the basis for further translational studies towards the importance of myoglobin for nitric oxide metabolism in humans.
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PMID:Assessment of the functional diversity of human myoglobin. 2242 79

Myoglobin (Mb) is an ideal scaffold protein for rational protein design mimicking native enzymes. We recently designed a nitrite reductase (NiR) based on sperm whale Mb by introducing an additional distal histidine (Leu29 to His29 mutation) and generating a distal tyrosine (Phe43 to Tyr43 mutation) in the heme pocket, namely L29H/F43Y Mb, to mimic the active site of cytochrome cd (1) NiR from Ps. aeruginosa that contains two distal histidines and one distal tyrosine. The molecular modeling and dynamics simulation study herein revealed that L29H/F43Y Mb has the necessary structural features of native cytochrome cd (1) NiR and can provide comparable interactions with nitrite as in native NiRs, which provides rationality for the protein design and guides the protein engineering. Additionally, the present study provides an insight into the relatively low NiR activity of Mb in biological systems.
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PMID:Rational design of a nitrite reductase based on myoglobin: a molecular modeling and dynamics simulation study. 2258 86