Flavohemoprotein

Details

Name
Flavohemoprotein
Synonyms
  • Flavohemoglobin
  • fsrB
  • Hemoglobin-like protein
  • HMP
  • hmpA
  • Nitric oxide dioxygenase
  • NO oxygenase
  • NOD
Gene Name
hmp
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0012051|Flavohemoprotein
MLDAQTIATVKATIPLLVETGPKLTAHFYDRMFTHNPELKEIFNMSNQRNGDQREALFNA
IAAYASNIENLPALLPAVEKIAQKHTSFQIKPEQYNIVGEHLLATLDEMFSPGQEVLDAW
GKAYGVLANVFINREAEIYNENASKAGGWEGTRDFRIVAKTPRSALITSFELEPVDGGAV
AEYRPGQYLGVWLKPEGFPHQEIRQYSLTRKPDGKGYRIAVKREEGGQVSNWLHNHANVG
DVVKLVAPAGDFFMAVADDTPVTLISAGVGQTPMLAMLDTLAKAGHTAQVNWFHAAENGD
VHAFADEVKELGQSLPRFTAHTWYRQPSEADRAKGQFDSEGLMDLSKLEGAFSDPTMQFY
LCGPVGFMQFTAKQLVDLGVKQENIHYECFGPHKVL
Number of residues
396
Molecular Weight
43867.385
Theoretical pI
5.57
GO Classification
Functions
FAD binding / fatty acid binding / heme binding / hydroperoxide reductase activity / metal ion binding / nitric oxide dioxygenase activity / oxygen binding / oxygen transporter activity
Processes
response to nitrosative stress / response to toxic substance
Components
cytoplasm
General Function
Oxygen transporter activity
Specific Function
Is involved in NO detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the bacterium from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress.In the presence of oxygen and NADH, HMP has NADH oxidase activity, which leads to the generation of superoxide and H(2)O(2), both in vitro and in vivo, and it has been suggested that HMP might act as an amplifier of superoxide stress. Under anaerobic conditions, HMP also exhibits nitric oxide reductase and FAD reductase activities. However, all these reactions are much lower than NOD activity.Various electron acceptors are also reduced by HMP in vitro, including dihydropterine, ferrisiderophores, ferric citrate, cytochrome c, nitrite, S-nitrosoglutathione, and alkylhydroperoxides. However, it is unknown if these reactions are of any biological significance in vivo.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0012052|Flavohemoprotein (hmp)
ATGCTTGACGCTCAAACCATCGCTACAGTAAAAGCCACCATCCCTTTACTGGTGGAAACG
GGGCCAAAGTTAACCGCCCATTTCTACGACCGTATGTTTACTCATAACCCAGAACTCAAA
GAAATTTTTAACATGAGTAACCAGCGTAATGGCGATCAACGTGAAGCCCTGTTTAACGCT
ATTGCCGCCTACGCCAGTAATATTGAAAACCTGCCTGCGCTGCTGCCAGCGGTAGAAAAA
ATCGCGCAGAAGCACACCAGCTTCCAGATCAAACCGGAACAGTACAACATCGTCGGTGAA
CACCTGTTGGCAACGCTGGACGAAATGTTCAGCCCGGGGCAGGAAGTGCTGGACGCGTGG
GGTAAAGCCTATGGTGTACTGGCTAATGTATTTATCAATCGCGAGGCGGAAATCTATAAC
GAAAACGCCAGCAAAGCCGGTGGTTGGGAAGGTACTCGCGATTTCCGCATTGTGGCTAAA
ACACCGCGCAGCGCGCTTATCACCAGCTTCGAACTGGAGCCGGTCGACGGTGGCGCAGTG
GCAGAATACCGTCCGGGGCAATATCTCGGCGTCTGGCTGAAGCCGGAAGGTTTCCCACAT
CAGGAAATTCGTCAGTACTCTTTGACTCGCAAACCGGATGGCAAAGGCTATCGTATTGCG
GTGAAACGCGAAGAGGGTGGGCAGGTATCCAACTGGTTGCACAATCACGCCAATGTTGGC
GATGTCGTGAAACTGGTCGCTCCGGCAGGTGATTTCTTTATGGCTGTCGCAGATGACACA
CCAGTGACGTTAATCTCTGCCGGTGTTGGTCAAACGCCAATGCTGGCAATGCTCGACACG
CTGGCAAAAGCAGGCCACACAGCACAAGTGAACTGGTTCCATGCGGCAGAAAATGGCGAT
GTTCACGCCTTTGCCGATGAAGTTAAGGAACTGGGGCAGTCACTGCCGCGCTTTACCGCG
CACACCTGGTATCGTCAGCCGAGCGAAGCCGATCGCGCTAAAGGTCAGTTTGATAGCGAA
GGTCTGATGGATTTGAGCAAACTGGAAGGTGCGTTCAGCGATCCGACAATGCAGTTCTAT
CTCTGCGGCCCGGTTGGCTTCATGCAGTTTACCGCGAAACAGTTAGTGGATCTGGGCGTG
AAGCAGGAAAACATTCATTACGAATGCTTTGGCCCGCATAAGGTGCTGTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP24232
UniProtKB Entry NameHMP_ECOLI
GenBank Gene IDX58872
General References
  1. Vasudevan SG, Armarego WL, Shaw DC, Lilley PE, Dixon NE, Poole RK: Isolation and nucleotide sequence of the hmp gene that encodes a haemoglobin-like protein in Escherichia coli K-12. Mol Gen Genet. 1991 Apr;226(1-2):49-58. [Article]
  2. Yamamoto Y, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kimura S, Kitagawa M, Makino K, Miki T, Mitsuhashi N, Mizobuchi K, Mori H, Nakade S, Nakamura Y, Nashimoto H, Oshima T, Oyama S, Saito N, Sampei G, Satoh Y, Sivasundaram S, Tagami H, Horiuchi T, et al.: Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. DNA Res. 1997 Apr 28;4(2):91-113. [Article]
  3. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  4. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  5. Plamann MD, Stauffer GV: Characterization of the Escherichia coli gene for serine hydroxymethyltransferase. Gene. 1983 Apr;22(1):9-18. [Article]
  6. Andrews SC, Shipley D, Keen JN, Findlay JB, Harrison PM, Guest JR: The haemoglobin-like protein (HMP) of Escherichia coli has ferrisiderophore reductase activity and its C-terminal domain shares homology with ferredoxin NADP+ reductases. FEBS Lett. 1992 May 18;302(3):247-52. [Article]
  7. Link AJ, Robison K, Church GM: Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12. Electrophoresis. 1997 Aug;18(8):1259-313. [Article]
  8. Gardner PR, Gardner AM, Martin LA, Salzman AL: Nitric oxide dioxygenase: an enzymic function for flavohemoglobin. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10378-83. [Article]
  9. Orii Y, Ioannidis N, Poole RK: The oxygenated flavohaemoglobin from Escherichia coli: evidence from photodissociation and rapid-scan studies for two kinetic and spectral forms. Biochem Biophys Res Commun. 1992 Aug 31;187(1):94-100. [Article]
  10. Eschenbrenner M, Coves J, Fontecave M: Ferric reductases in Escherichia coli: the contribution of the haemoglobin-like protein. Biochem Biophys Res Commun. 1994 Jan 14;198(1):127-31. [Article]
  11. Vasudevan SG, Tang P, Dixon NE, Poole RK: Distribution of the flavohaemoglobin, HMP, between periplasm and cytoplasm in Escherichia coli. FEMS Microbiol Lett. 1995 Jan 15;125(2-3):219-24. [Article]
  12. Membrillo-Hernandez J, Ioannidis N, Poole RK: The flavohaemoglobin (HMP) of Escherichia coli generates superoxide in vitro and causes oxidative stress in vivo. FEBS Lett. 1996 Mar 11;382(1-2):141-4. [Article]
  13. Poole RK, Anjum MF, Membrillo-Hernandez J, Kim SO, Hughes MN, Stewart V: Nitric oxide, nitrite, and Fnr regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12. J Bacteriol. 1996 Sep;178(18):5487-92. [Article]
  14. Poole RK, Ioannidis N, Orii Y: Reactions of the Escherichia coli flavohaemoglobin (Hmp) with NADH and near-micromolar oxygen: oxygen affinity of NADH oxidase activity. Microbiology. 1996 May;142 ( Pt 5):1141-8. [Article]
  15. Membrillo-Hernandez J, Kim SO, Cook GM, Poole RK: Paraquat regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12 is SoxRS independent but modulated by sigma S. J Bacteriol. 1997 May;179(10):3164-70. [Article]
  16. Poole RK, Rogers NJ, D'mello RA, Hughes MN, Orii Y: Escherichia coli flavohaemoglobin (Hmp) reduces cytochrome c and Fe(III)-hydroxamate K by electron transfer from NADH via FAD: sensitivity of oxidoreductase activity to haem-bound dioxygen. Microbiology. 1997 May;143 ( Pt 5):1557-65. [Article]
  17. Anjum MF, Ioannidis N, Poole RK: Response of the NAD(P)H-oxidising flavohaemoglobin (Hmp) to prolonged oxidative stress and implications for its physiological role in Escherichia coli. FEMS Microbiol Lett. 1998 Sep 15;166(2):219-23. [Article]
  18. Gardner PR, Costantino G, Salzman AL: Constitutive and adaptive detoxification of nitric oxide in Escherichia coli. Role of nitric-oxide dioxygenase in the protection of aconitase. J Biol Chem. 1998 Oct 9;273(41):26528-33. [Article]
  19. Membrillo-Hernandez J, Coopamah MD, Channa A, Hughes MN, Poole RK: A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region. Mol Microbiol. 1998 Aug;29(4):1101-12. [Article]
  20. Hausladen A, Gow AJ, Stamler JS: Nitrosative stress: metabolic pathway involving the flavohemoglobin. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14100-5. [Article]
  21. Kim SO, Orii Y, Lloyd D, Hughes MN, Poole RK: Anoxic function for the Escherichia coli flavohaemoglobin (Hmp): reversible binding of nitric oxide and reduction to nitrous oxide. FEBS Lett. 1999 Feb 26;445(2-3):389-94. [Article]
  22. Membrillo-Hernandez J, Coopamah MD, Anjum MF, Stevanin TM, Kelly A, Hughes MN, Poole RK: The flavohemoglobin of Escherichia coli confers resistance to a nitrosating agent, a "Nitric oxide Releaser," and paraquat and is essential for transcriptional responses to oxidative stress. J Biol Chem. 1999 Jan 8;274(2):748-54. [Article]
  23. Gardner AM, Martin LA, Gardner PR, Dou Y, Olson JS: Steady-state and transient kinetics of Escherichia coli nitric-oxide dioxygenase (flavohemoglobin). The B10 tyrosine hydroxyl is essential for dioxygen binding and catalysis. J Biol Chem. 2000 Apr 28;275(17):12581-9. [Article]
  24. Gardner PR, Gardner AM, Martin LA, Dou Y, Li T, Olson JS, Zhu H, Riggs AF: Nitric-oxide dioxygenase activity and function of flavohemoglobins. sensitivity to nitric oxide and carbon monoxide inhibition. J Biol Chem. 2000 Oct 13;275(41):31581-7. [Article]
  25. Stevanin TM, Ioannidis N, Mills CE, Kim SO, Hughes MN, Poole RK: Flavohemoglobin Hmp affords inducible protection for Escherichia coli respiration, catalyzed by cytochromes bo' or bd, from nitric oxide. J Biol Chem. 2000 Nov 17;275(46):35868-75. [Article]
  26. Mills CE, Sedelnikova S, Soballe B, Hughes MN, Poole RK: Escherichia coli flavohaemoglobin (Hmp) with equistoichiometric FAD and haem contents has a low affinity for dioxygen in the absence or presence of nitric oxide. Biochem J. 2001 Jan 15;353(Pt 2):207-13. [Article]
  27. Bonamore A, Chiancone E, Boffi A: The distal heme pocket of Escherichia coli flavohemoglobin probed by infrared spectroscopy. Biochim Biophys Acta. 2001 Oct 18;1549(2):174-8. [Article]
  28. Mukai M, Mills CE, Poole RK, Yeh SR: Flavohemoglobin, a globin with a peroxidase-like catalytic site. J Biol Chem. 2001 Mar 9;276(10):7272-7. Epub 2000 Nov 22. [Article]
  29. Hausladen A, Gow A, Stamler JS: Flavohemoglobin denitrosylase catalyzes the reaction of a nitroxyl equivalent with molecular oxygen. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10108-12. Epub 2001 Aug 21. [Article]
  30. Gardner AM, Gardner PR: Flavohemoglobin detoxifies nitric oxide in aerobic, but not anaerobic, Escherichia coli. Evidence for a novel inducible anaerobic nitric oxide-scavenging activity. J Biol Chem. 2002 Mar 8;277(10):8166-71. Epub 2001 Dec 18. [Article]
  31. Bonamore A, Farina A, Gattoni M, Schinina ME, Bellelli A, Boffi A: Interaction with membrane lipids and heme ligand binding properties of Escherichia coli flavohemoglobin. Biochemistry. 2003 May 20;42(19):5792-801. [Article]
  32. Bonamore A, Gentili P, Ilari A, Schinina ME, Boffi A: Escherichia coli flavohemoglobin is an efficient alkylhydroperoxide reductase. J Biol Chem. 2003 Jun 20;278(25):22272-7. Epub 2003 Mar 27. [Article]
  33. Corker H, Poole RK: Nitric oxide formation by Escherichia coli. Dependence on nitrite reductase, the NO-sensing regulator Fnr, and flavohemoglobin Hmp. J Biol Chem. 2003 Aug 22;278(34):31584-92. Epub 2003 Jun 3. [Article]
  34. Hernandez-Urzua E, Mills CE, White GP, Contreras-Zentella ML, Escamilla E, Vasudevan SG, Membrillo-Hernandez J, Poole RK: Flavohemoglobin Hmp, but not its individual domains, confers protection from respiratory inhibition by nitric oxide in Escherichia coli. J Biol Chem. 2003 Sep 12;278(37):34975-82. Epub 2003 Jun 24. [Article]
  35. Ilari A, Bonamore A, Farina A, Johnson KA, Boffi A: The X-ray structure of ferric Escherichia coli flavohemoglobin reveals an unexpected geometry of the distal heme pocket. J Biol Chem. 2002 Jun 28;277(26):23725-32. Epub 2002 Apr 18. [Article]
  36. Poole RK, Hughes MN: New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress. Mol Microbiol. 2000 May;36(4):775-83. [Article]
  37. Frey AD, Kallio PT: Bacterial hemoglobins and flavohemoglobins: versatile proteins and their impact on microbiology and biotechnology. FEMS Microbiol Rev. 2003 Oct;27(4):525-45. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails