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Escherichia coli K-12 substr. MG1655 Enzyme: multicopper oxidase with role in copper homeostasis



Gene: cueO Accession Numbers: EG12318 (EcoCyc), b0123, ECK0122

Synonyms: yacK, MCO

Regulation Summary Diagram: ?

Summary:
CueO multicopper oxidase is a copper-stimulated phenoloxidase and ferroxidase [Kim01d] that plays a role in copper homeostasis [Grass01] during aerobiosis [Outten01]. CueO has been observed to offer protective effects from copper-mediated damage [Grass01a]. In the presence of copper, CueO can oxidize and thus inactivate the iron siderophores 2,3-dihydroxybenzoate and enterobactin in vitro [Kim01d, Grass04]. A mixture of enterobactin and copper is toxic, and ferric enterobactin may be the natural substrate of CueO in vivo; thus, CueO may play a central role as an interface between copper detoxification and iron homeostasis [Grass04]. The purified protein was also shown to have cuprous oxidase activity in vitro [Singh04]. Studies using copper radioisotopes have shown that CueO is the only major form of soluble protein-bound copper in E. coli [Sevcenco09].

CueO is translocated to the periplasm via the Tat pathway [Grass01a, DeLisa04]. Published reports disagree as to whether CueO binds four [Grass01a] or six [Kim01d] atoms of copper per monomer. The enzyme exhibits characteristics of blue copper oxidases [Grass01a]. Copper is incorporated sequentially to the three types of binding sites in CueO [Galli04]. Crystal structures of the enzyme are presented at 1.4 Å [Roberts02a] and 1.7 Å [Roberts03a] resolution.

Phenoloxidase activity of CueO was demonstrated against substrates including p-phenylenediamine [Grass01a], 2,6-dimethoxyphenol [Grass01a, Solano01], and iron siderophores including 2,3-dihydroxybenzoate, enterobactin, and 3-hydroxyanthranilate [Kim01d]. Optimal reaction conditions are described [Roberts02a] and details of the reaction mechanism are discussed [Roberts02a, Roberts03a].

PcoA and CueO exhibit functional redundancy [Lee02c].

Regulation has been described [Outten00].

Review: [Rensing03]

Citations: [Merlin02]

Locations: periplasmic space

Map Position: [137,083 -> 138,633] (2.95 centisomes)
Length: 1551 bp / 516 aa

Molecular Weight of Polypeptide: 56.556 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0000430 , DIP:DIP-11178N , EchoBASE:EB2223 , EcoGene:EG12318 , EcoliWiki:b0123 , ModBase:P36649 , OU-Microarray:b0123 , PortEco:cueO , PR:PRO_000022347 , Pride:P36649 , Protein Model Portal:P36649 , RefSeq:NP_414665 , RegulonDB:EG12318 , SMR:P36649 , String:511145.b0123 , UniProt:P36649

Relationship Links: InterPro:IN-FAMILY:IPR001117 , InterPro:IN-FAMILY:IPR002355 , InterPro:IN-FAMILY:IPR006311 , InterPro:IN-FAMILY:IPR008972 , InterPro:IN-FAMILY:IPR011706 , InterPro:IN-FAMILY:IPR011707 , PDB:Structure:1KV7 , PDB:Structure:1N68 , PDB:Structure:1PF3 , PDB:Structure:2FQD , PDB:Structure:2FQE , PDB:Structure:2FQF , PDB:Structure:2FQG , PDB:Structure:2YXV , PDB:Structure:2YXW , PDB:Structure:3NSC , PDB:Structure:3NSD , PDB:Structure:3NSF , PDB:Structure:3NSY , PDB:Structure:3NT0 , PDB:Structure:3OD3 , PDB:Structure:3PAU , PDB:Structure:3PAV , PDB:Structure:3QQX , PDB:Structure:3UAA , PDB:Structure:3UAB , PDB:Structure:3UAC , PDB:Structure:3UAD , PDB:Structure:3UAE , PDB:Structure:4E9P , PDB:Structure:4E9Q , PDB:Structure:4E9R , PDB:Structure:4E9S , PDB:Structure:4E9T , PDB:Structure:4EF3 , Pfam:IN-FAMILY:PF00394 , Pfam:IN-FAMILY:PF07731 , Pfam:IN-FAMILY:PF07732 , Prosite:IN-FAMILY:PS00080 , Prosite:IN-FAMILY:PS51318

In Paralogous Gene Group: 41 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0005507 - copper ion binding Inferred from experiment Inferred by computational analysis [GOA01, Grass01a]
GO:0016722 - oxidoreductase activity, oxidizing metal ions Inferred from experiment [Grass01a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment Inferred by computational analysis [DiazMejia09, Han13, Grass01a]
GO:0042597 - periplasmic space Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, Grass01a]

MultiFun Terms: cell processes adaptations other (mechanical, nutritional, oxidative stress)
cell processes protection detoxification
metabolism

Essentiality data for cueO knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Enzymatic reaction of: cuprous oxidase (multicopper oxidase with role in copper homeostasis)

EC Number: 1.16.3.-

4 Cu+[periplasmic space] + 4 H+[periplasmic space] + oxygen[periplasmic space] <=> 4 Cu2+[periplasmic space] + 2 H2O[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.


Enzymatic reaction of: 2,3-dihydroxybenzoate:oxygen oxidoreductase (multicopper oxidase with role in copper homeostasis)

2,3-dihydroxybenzoate[periplasmic space] + oxygen[periplasmic space] <=> 2-carboxymuconate[periplasmic space] + 2 H+[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.


Enzymatic reaction of: ferroxidase (multicopper oxidase with role in copper homeostasis)

EC Number: 1.16.3.1

4 Fe2+[periplasmic space] + 4 H+[periplasmic space] + oxygen[periplasmic space] <=> 4 Fe3+[periplasmic space] + 2 H2O[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.


Sequence Features

Feature Class Location Citations Comment
Signal-Sequence 1 -> 28
[Link97, UniProt11]
UniProt: Tat-type signal.
Chain 29 -> 516
[UniProt09]
UniProt: Blue copper oxidase cueO;
Conserved-Region 67 -> 163
[UniProt09]
UniProt: Plastocyanin-like 1;
Metal-Binding-Site 101
[UniProt10a]
UniProt: Copper 1; type 2;
Metal-Binding-Site 103
[UniProt10a]
UniProt: Copper 2; type 3;
Metal-Binding-Site 141
[UniProt10a]
UniProt: Copper 2; type 3;
Metal-Binding-Site 143
[UniProt10a]
UniProt: Copper 3; type 3;
Conserved-Region 164 -> 410
[UniProt09]
UniProt: Plastocyanin-like 2;
Protein-Segment 355 -> 400
[UniProt09]
UniProt: Met-rich; Sequence Annotation Type: compositionally biased region;
Conserved-Region 411 -> 516
[UniProt09]
UniProt: Plastocyanin-like 3;
Metal-Binding-Site 443
[UniProt10a]
UniProt: Copper 4; type 1;
Metal-Binding-Site 446
[UniProt10a]
UniProt: Copper 1; type 2;
Metal-Binding-Site 448
[UniProt10a]
UniProt: Copper 3; type 3;
Metal-Binding-Site 499
[UniProt10a]
UniProt: Copper 3; type 3;
Mutagenesis-Variant 500 -> 501
[Grass01a, UniProt11]
Alternate sequence: CH → SR; UniProt: Residual activity and loss of resistance to copper.
Metal-Binding-Site 500
[UniProt10a]
UniProt: Copper 4; type 1;
Metal-Binding-Site 501
[UniProt10a]
UniProt: Copper 2; type 3;
Metal-Binding-Site 505
[UniProt10a]
UniProt: Copper 4; type 1;
Metal-Binding-Site 510
[UniProt10a]
UniProt: Copper 4; type 1;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b0123 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12318; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

DeLisa04: DeLisa MP, Lee P, Palmer T, Georgiou G (2004). "Phage shock protein PspA of Escherichia coli relieves saturation of protein export via the Tat pathway." J Bacteriol 186(2);366-73. PMID: 14702305

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Galli04: Galli I, Musci G, Bonaccorsi di Patti MC (2004). "Sequential reconstitution of copper sites in the multicopper oxidase CueO." J Biol Inorg Chem 9(1);90-5. PMID: 14648285

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grass01: Grass G, Rensing C (2001). "Genes involved in copper homeostasis in Escherichia coli." J Bacteriol 183(6);2145-7. PMID: 11222619

Grass01a: Grass G, Rensing C (2001). "CueO is a multi-copper oxidase that confers copper tolerance in Escherichia coli." Biochem Biophys Res Commun 286(5);902-8. PMID: 11527384

Grass04: Grass G, Thakali K, Klebba PE, Thieme D, Muller A, Wildner GF, Rensing C (2004). "Linkage between catecholate siderophores and the multicopper oxidase CueO in Escherichia coli." J Bacteriol 186(17);5826-33. PMID: 15317788

Han13: Han MJ, Kim JY, Kim JA (2013). "Comparison of the large-scale periplasmic proteomes of the Escherichia coli K-12 and B strains." J Biosci Bioeng. PMID: 24140104

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kim01d: Kim C, Lorenz WW, Hoopes JT, Dean JF (2001). "Oxidation of phenolate siderophores by the multicopper oxidase encoded by the Escherichia coli yacK gene." J Bacteriol 183(16);4866-75. PMID: 11466290

Lee02c: Lee SM, Grass G, Rensing C, Barrett SR, Yates CJ, Stoyanov JV, Brown NL (2002). "The Pco proteins are involved in periplasmic copper handling in Escherichia coli." Biochem Biophys Res Commun 295(3);616-20. PMID: 12099683

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

Merlin02: Merlin C, McAteer S, Masters M (2002). "Tools for characterization of Escherichia coli genes of unknown function." J Bacteriol 184(16);4573-81. PMID: 12142427

Outten00: Outten FW, Outten CE, Hale J, O'Halloran TV (2000). "Transcriptional activation of an Escherichia coli copper efflux regulon by the chromosomal MerR homologue, cueR." J Biol Chem 275(40);31024-9. PMID: 10915804

Outten01: Outten FW, Huffman DL, Hale JA, O'Halloran TV (2001). "The independent cue and cus systems confer copper tolerance during aerobic and anaerobic growth in Escherichia coli." J Biol Chem 276(33);30670-7. PMID: 11399769

Rensing03: Rensing C, Grass G (2003). "Escherichia coli mechanisms of copper homeostasis in a changing environment." FEMS Microbiol Rev 27(2-3);197-213. PMID: 12829268

Roberts02a: Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT, Tollin G, Rensing C, Montfort WR (2002). "Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli." Proc Natl Acad Sci U S A 99(5);2766-71. PMID: 11867755

Roberts03a: Roberts SA, Wildner GF, Grass G, Weichsel A, Ambrus A, Rensing C, Montfort WR (2003). "A labile regulatory copper ion lies near the T1 copper site in the multicopper oxidase CueO." J Biol Chem 278(34):31958-63. PMID: 12794077

Sevcenco09: Sevcenco AM, Krijger GC, Pinkse MW, Verhaert PD, Hagen WR, Hagedoorn PL (2009). "Development of a generic approach to native metalloproteomics: application to the quantitative identification of soluble copper proteins in Escherichia coli." J Biol Inorg Chem 14(4);631-40. PMID: 19205756

Singh04: Singh SK, Grass G, Rensing C, Montfort WR (2004). "Cuprous Oxidase Activity of CueO from Escherichia coli." J Bacteriol 186(22);7815-7. PMID: 15516598

Solano01: Solano F, Lucas-Elio P, Lopez-Serrano D, Fernandez E, Sanchez-Amat A (2001). "Dimethoxyphenol oxidase activity of different microbial blue multicopper proteins." FEMS Microbiol Lett 204(1);175-81. PMID: 11682198

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

Other References Related to Gene Regulation

Yamamoto05a: Yamamoto K, Ishihama A (2005). "Transcriptional response of Escherichia coli to external copper." Mol Microbiol 56(1);215-27. PMID: 15773991


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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