Nitric oxide dioxygenase: an enzymic function for flavohemoglobin.
Nitric oxide (NO*) is a toxin, and various life forms appear to have evolved strategies for its detoxification. NO*-resistant mutants of Escherichia coli were isolated that rapidly consumed NO*. An NO*-converting activity was reconstituted in extracts that required NADPH, FAD, and O2, was cyanide-sensitive, and produced NO3-. This nitric oxide dioxygenase (NOD) contained 19 of 20 N-terminal amino acids identical to those of the E. coli flavohemoglobin. Furthermore, NOD activity was produced by the flavohemoglobin gene and was inducible by NO*. Flavohemoglobin/NOD-deficient mutants were also sensitive to growth inhibition by gaseous NO*. The results identify a function for the evolutionarily conserved flavohemoglobins and, moreover, suggest that NO* detoxification may be a more ancient function for the widely distributed hemoglobins, and associated methemoglobin reductases, than dioxygen transport and storage.
Gardner
P R
PR
Division of Critical Care Medicine, Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. gardp0@chmcc.org
Gardner
A M
AM
Martin
L A
LA
Salzman
A L
AL
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D002474:Cell-Free System; D002852:Chromatography, Ion Exchange; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006420:Hemeproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*
D001426:Bacterial Proteins; D017931:DNA Primers; D006420:Hemeproteins; C086193:flavohemoprotein, Bacteria; D010105:Oxygenases; C114415:nitric oxide dioxygenase