Flavohemoprotein (P24232)

Identification
Name:Flavohemoprotein
Synonyms:
  • Flavohemoglobin
  • HMP
  • Hemoglobin-like protein
  • Nitric oxide dioxygenase
  • NO oxygenase
  • NOD
Gene Name:hmp
Enzyme Class:
Biological Properties
General Function:Involved in oxidoreductase activity
Specific Function: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
Cellular Location:Cytoplasm.
SMPDB Pathways:Not Available
KEGG Pathways:Not Available
KEGG Reactions:
1.0Thumb+2.0Thumb+1.0Thumb+1.0Thumb ↔ 2.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb
1.0Nitric oxide + 2.0Oxygen + 1.0NADH + 1.0NADPH ↔ 2.0Nitrate + 1.0NAD + 1.0NADP + 1.0Hydrogen ion
ReactionCard
EcoCyc Reactions:
1.0NAD(P)++1.0Thumb ↔ 1.0NAD(P)H+1.0Thumb+1.0Thumb
1.0NAD(P)+ + 1.0Tetrahydropteridine ↔ 1.0NAD(P)H + 1.06,7-Dihydropteridine + 1.0Hydrogen ion
ReactionCard
1.0NAD(P)H+1.0Thumb+1.0Thumb → 1.0NAD(P)++1.0Thumb+1.0Thumb
1.0NAD(P)H + 1.0Nitric oxide + 1.0Oxygen → 1.0NAD(P)+ + 1.0Nitrate + 1.0Hydrogen ion
ReactionCard
Complex Reactions:
1.0Thumb+2.0Thumb+2.0Thumb → 1.0Thumb+1.0Thumb+2.0Thumb
1.0NADH + 2.0Nitric oxide + 2.0Oxygen → 1.0Hydrogen ion + 1.0NAD + 2.0Nitrate
ReactionCard
1.0Thumb+2.0Thumb+2.0Thumb → 1.0Thumb+1.0Thumb+2.0Thumb
1.0NADPH + 2.0Nitric oxide + 2.0Oxygen → 1.0Hydrogen ion + 1.0NADP + 2.0Nitrate
ReactionCard
2.0Thumb+2.0Thumb+1.0NAD(P)H → 2.0Thumb+1.0NAD(P)(+)
2.0Nitric oxide + 2.0Oxygen + 1.0NAD(P)H → 2.0Nitrate + 1.0NAD(P)(+)
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB014416,7-DihydropteridineMetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB00902NADMetaboCard
ECMDB01487NADHMetaboCard
ECMDB00217NADPMetaboCard
ECMDB04111NADPHMetaboCard
ECMDB02878NitrateMetaboCard
ECMDB03378Nitric oxideMetaboCard
ECMDB04124OxygenMetaboCard
ECMDB01216TetrahydropteridineMetaboCard
GO Classification:
Function
binding
catalytic activity
cation binding
heme binding
ion binding
iron ion binding
metal ion binding
oxidoreductase activity
oxygen binding
transition metal ion binding
Process
establishment of localization
gas transport
metabolic process
oxidation reduction
oxygen transport
transport
Gene Properties
Blattner:b2552
Gene OrientationClockwise
Centisome Percentage:57.85
Left Sequence End2683857
Right Sequence End2685047
Gene Sequence:
>1191 bp
ATGACAACAAACACTGTTTCCCGCAAAGTGGCGTGGCTACGGGTCGTTACGCTGGCAGTC
GCCGCCTTCATCTTCAACACCACCGAATTTGTCCCTGTTGGCCTGCTCTCTGACATTGCG
CAAAGTTTTCACATGCAAACCGCTCAGGTCGGCATCATGTTGACCATTTACGCATGGGTA
GTAGCGCTAATGTCATTGCCTTTTATGTTAATGACCAGTCAGGTTGAACGGCGCAAATTA
CTGATCTGCCTGTTTGTGGTGTTTATTGCCAGCCACGTACTGTCGTTTTTGTCGTGGAGC
TTTACCGTTCTGGTGATCAGTCGCATTGGTGTGGCTTTTGCACATGCGATTTTCTGGTCG
ATTACGGCGTCTCTGGCGATCCGTATGGCTCCGGCCGGGAAGCGAGCACAGGCATTGAGT
TTAATTGCCACCGGTACAGCACTGGCGATGGTCTTAGGTTTACCTCTCGGGCGCATTGTG
GGCCAGTATTTCGGTTGGCGAATGACCTTCTTCGCGATTGGTATTGGGGCGCTTATCACC
CTTTTGTGCCTGATTAAGTTACTTCCCTTACTGCCCAGTGAGCATTCCGGTTCACTGAAA
AGCCTCCCGCTATTGTTCCGCCGCCCGGCATTGATGAGCATTTATTTGTTAACTGTGGTG
GTTGTCACCGCCCATTACACGGCATACAGCTATATCGAGCCTTTTGTACAAAACATTGCG
GGATTCAGCGCCAACTTTGCCACGGCATTACTGTTATTACTCGGTGGTGCGGGCATTATT
GGCAGCGTGATTTTCGGTAAACTGGGTAATCAGTATGCGTCTGCGTTGGTGAGTACGGCG
ATTGCGCTGTTGCTGGTGTGCCTGGCATTGCTGTTACCTGCGGCGAACAGTGAAATACAC
CTCGGGGTGCTGAGTATTTTCTGGGGGATCGCGATGATGATCATCGGGCTTGGTATGCAG
GTTAAAGTGCTGGCGCTGGCACCAGATGCTACCGACGTCGCGATGGCGCTATTCTCCGGC
ATATTTAATATTGGAATCGGGGCGGGTGCGTTGGTAGGTAATCAGGTGAGTTTGCACTGG
TCAATGTCGATGATTGGTTATGTGGGCGCGGTGCCTGCTTTTGCCGCGTTAATTTGGTCA
ATCATTATATTTCGCCGCTGGCCAGTGACACTCGAAGAACAGACGCAATAG
Protein Properties
Pfam Domain Function:
Protein Residues:396
Protein Molecular Weight:43867
Protein Theoretical pI:6
PDB File:1GVH
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Flavohemoprotein
MLDAQTIATVKATIPLLVETGPKLTAHFYDRMFTHNPELKEIFNMSNQRNGDQREALFNA
IAAYASNIENLPALLPAVEKIAQKHTSFQIKPEQYNIVGEHLLATLDEMFSPGQEVLDAW
GKAYGVLANVFINREAEIYNENASKAGGWEGTRDFRIVAKTPRSALITSFELEPVDGGAV
AEYRPGQYLGVWLKPEGFPHQEIRQYSLTRKPDGKGYRIAVKREEGGQVSNWLHNHANVG
DVVKLVAPAGDFFMAVADDTPVTLISAGVGQTPMLAMLDTLAKAGHTAQVNWFHAAENGD
VHAFADEVKELGQSLPRFTAHTWYRQPSEADRAKGQFDSEGLMDLSKLEGAFSDPTMQFY
LCGPVGFMQFTAKQLVDLGVKQENIHYECFGPHKVL
References
External Links:
ResourceLink
Uniprot ID:P24232
Uniprot Name:HMP_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:1742501
PDB ID:1GVH
Ecogene ID:EG10456
Ecocyc:EG10456
ColiBase:b2552
Kegg Gene:b2552
EchoBASE ID:EB0451
CCDB:HMP_ECOLI
BacMap:16130477
General Reference:
  • Andrews, S. C., Shipley, D., Keen, J. N., Findlay, J. B., Harrison, P. M., Guest, J. R. (1992). "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 302:247-252. Pubmed: 1601132
  • Anjum, M. F., Ioannidis, N., Poole, R. K. (1998). "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 166:219-223. Pubmed: 9770277
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Bonamore, A., Chiancone, E., Boffi, A. (2001). "The distal heme pocket of Escherichia coli flavohemoglobin probed by infrared spectroscopy." Biochim Biophys Acta 1549:174-178. Pubmed: 11690654
  • Bonamore, A., Farina, A., Gattoni, M., Schinina, M. E., Bellelli, A., Boffi, A. (2003). "Interaction with membrane lipids and heme ligand binding properties of Escherichia coli flavohemoglobin." Biochemistry 42:5792-5801. Pubmed: 12741837
  • Bonamore, A., Gentili, P., Ilari, A., Schinina, M. E., Boffi, A. (2003). "Escherichia coli flavohemoglobin is an efficient alkylhydroperoxide reductase." J Biol Chem 278:22272-22277. Pubmed: 12663656
  • Corker, H., Poole, R. K. (2003). "Nitric oxide formation by Escherichia coli. Dependence on nitrite reductase, the NO-sensing regulator Fnr, and flavohemoglobin Hmp." J Biol Chem 278:31584-31592. Pubmed: 12783887
  • Eschenbrenner, M., Coves, J., Fontecave, M. (1994). "Ferric reductases in Escherichia coli: the contribution of the haemoglobin-like protein." Biochem Biophys Res Commun 198:127-131. Pubmed: 8292013
  • Frey, A. D., Kallio, P. T. (2003). "Bacterial hemoglobins and flavohemoglobins: versatile proteins and their impact on microbiology and biotechnology." FEMS Microbiol Rev 27:525-545. Pubmed: 14550944
  • Gardner, A. M., Gardner, P. R. (2002). "Flavohemoglobin detoxifies nitric oxide in aerobic, but not anaerobic, Escherichia coli. Evidence for a novel inducible anaerobic nitric oxide-scavenging activity." J Biol Chem 277:8166-8171. Pubmed: 11751864
  • Gardner, A. M., Martin, L. A., Gardner, P. R., Dou, Y., Olson, J. S. (2000). "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 275:12581-12589. Pubmed: 10777548
  • Gardner, P. R., Costantino, G., Salzman, A. L. (1998). "Constitutive and adaptive detoxification of nitric oxide in Escherichia coli. Role of nitric-oxide dioxygenase in the protection of aconitase." J Biol Chem 273:26528-26533. Pubmed: 9756889
  • Gardner, P. R., Gardner, A. M., Martin, L. A., Dou, Y., Li, T., Olson, J. S., Zhu, H., Riggs, A. F. (2000). "Nitric-oxide dioxygenase activity and function of flavohemoglobins. sensitivity to nitric oxide and carbon monoxide inhibition." J Biol Chem 275:31581-31587. Pubmed: 10922365
  • Gardner, P. R., Gardner, A. M., Martin, L. A., Salzman, A. L. (1998). "Nitric oxide dioxygenase: an enzymic function for flavohemoglobin." Proc Natl Acad Sci U S A 95:10378-10383. Pubmed: 9724711
  • Hausladen, A., Gow, A. J., Stamler, J. S. (1998). "Nitrosative stress: metabolic pathway involving the flavohemoglobin." Proc Natl Acad Sci U S A 95:14100-14105. Pubmed: 9826660
  • Hausladen, A., Gow, A., Stamler, J. S. (2001). "Flavohemoglobin denitrosylase catalyzes the reaction of a nitroxyl equivalent with molecular oxygen." Proc Natl Acad Sci U S A 98:10108-10112. Pubmed: 11517313
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Hernandez-Urzua, E., Mills, C. E., White, G. P., Contreras-Zentella, M. L., Escamilla, E., Vasudevan, S. G., Membrillo-Hernandez, J., Poole, R. K. (2003). "Flavohemoglobin Hmp, but not its individual domains, confers protection from respiratory inhibition by nitric oxide in Escherichia coli." J Biol Chem 278:34975-34982. Pubmed: 12826671
  • Ilari, A., Bonamore, A., Farina, A., Johnson, K. A., Boffi, A. (2002). "The X-ray structure of ferric Escherichia coli flavohemoglobin reveals an unexpected geometry of the distal heme pocket." J Biol Chem 277:23725-23732. Pubmed: 11964402
  • Kim, S. O., Orii, Y., Lloyd, D., Hughes, M. N., Poole, R. K. (1999). "Anoxic function for the Escherichia coli flavohaemoglobin (Hmp): reversible binding of nitric oxide and reduction to nitrous oxide." FEBS Lett 445:389-394. Pubmed: 10094495
  • Link, A. J., Robison, K., Church, G. M. (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18:1259-1313. Pubmed: 9298646
  • Membrillo-Hernandez, J., Coopamah, M. D., Anjum, M. F., Stevanin, T. M., Kelly, A., Hughes, M. N., Poole, R. K. (1999). "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 274:748-754. Pubmed: 9873011
  • Membrillo-Hernandez, J., Coopamah, M. D., Channa, A., Hughes, M. N., Poole, R. K. (1998). "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 29:1101-1112. Pubmed: 9767577
  • Membrillo-Hernandez, J., Ioannidis, N., Poole, R. K. (1996). "The flavohaemoglobin (HMP) of Escherichia coli generates superoxide in vitro and causes oxidative stress in vivo." FEBS Lett 382:141-144. Pubmed: 8612736
  • Membrillo-Hernandez, J., Kim, S. O., Cook, G. M., Poole, R. K. (1997). "Paraquat regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12 is SoxRS independent but modulated by sigma S." J Bacteriol 179:3164-3170. Pubmed: 9150210
  • Mills, C. E., Sedelnikova, S., Soballe, B., Hughes, M. N., Poole, R. K. (2001). "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 353:207-213. Pubmed: 11139382
  • Mukai, M., Mills, C. E., Poole, R. K., Yeh, S. R. (2001). "Flavohemoglobin, a globin with a peroxidase-like catalytic site." J Biol Chem 276:7272-7277. Pubmed: 11092893
  • Orii, Y., Ioannidis, N., Poole, R. K. (1992). "The oxygenated flavohaemoglobin from Escherichia coli: evidence from photodissociation and rapid-scan studies for two kinetic and spectral forms." Biochem Biophys Res Commun 187:94-100. Pubmed: 1325799
  • Plamann, M. D., Stauffer, G. V. (1983). "Characterization of the Escherichia coli gene for serine hydroxymethyltransferase." Gene 22:9-18. Pubmed: 6190704
  • Poole, R. K., Anjum, M. F., Membrillo-Hernandez, J., Kim, S. O., Hughes, M. N., Stewart, V. (1996). "Nitric oxide, nitrite, and Fnr regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12." J Bacteriol 178:5487-5492. Pubmed: 8808940
  • Poole, R. K., Hughes, M. N. (2000). "New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress." Mol Microbiol 36:775-783. Pubmed: 10844666
  • Poole, R. K., Ioannidis, N., Orii, Y. (1996). "Reactions of the Escherichia coli flavohaemoglobin (Hmp) with NADH and near-micromolar oxygen: oxygen affinity of NADH oxidase activity." Microbiology 142 ( Pt 5):1141-1148. Pubmed: 8704956
  • Poole, R. K., Rogers, N. J., D'mello, R. A., Hughes, M. N., Orii, Y. (1997). "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 143 ( Pt 5):1557-1565. Pubmed: 9168606
  • Stevanin, T. M., Ioannidis, N., Mills, C. E., Kim, S. O., Hughes, M. N., Poole, R. K. (2000). "Flavohemoglobin Hmp affords inducible protection for Escherichia coli respiration, catalyzed by cytochromes bo' or bd, from nitric oxide." J Biol Chem 275:35868-35875. Pubmed: 10915782
  • Vasudevan, S. G., Armarego, W. L., Shaw, D. C., Lilley, P. E., Dixon, N. E., Poole, R. K. (1991). "Isolation and nucleotide sequence of the hmp gene that encodes a haemoglobin-like protein in Escherichia coli K-12." Mol Gen Genet 226:49-58. Pubmed: 2034230
  • Vasudevan, S. G., Tang, P., Dixon, N. E., Poole, R. K. (1995). "Distribution of the flavohaemoglobin, HMP, between periplasm and cytoplasm in Escherichia coli." FEMS Microbiol Lett 125:219-224. Pubmed: 7875569
  • 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, a. l. .. (1997). "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 4:91-113. Pubmed: 9205837