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.
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
P R
PR
Gardner
A M
AM
Gardner
L A
LA
Martin
A L
AL
Salzman
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