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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Enzyme: formate dehydrogenase H

Gene: fdhF Accession Numbers: EG10285 (MetaCyc), b4079, ECK4072

Synonyms: chlF, FDH-H

Species: Escherichia coli K-12 substr. MG1655

Component of: formate hydrogenlyase complex

Summary:
Formate dehydrogenase-H is one of three membrane-associated formate dehydrogenase isoenzymes in E. coli [Sawers94]. All are functional in the anaerobic metabolism of the organism. Formate dehydrogenase-H (FDH-H) is located in the cytoplasm and together with hydrogenase-3, FDH-H forms the formate-hydrogen lyase complex [Axley90, Sawers94].

The enzyme is oxygen sensitive and contains selenium as selenocysteine incorporated cotranslationally at the position of an in-frame UGA stop codon in the FdhF open reading frame [Zinoni86].

A crystal structure of FDH-H has been solved at 2.3 Å resolution, confirming the presence of a [4Fe-4S] cluster, coordination of the Mo cofactor by selenocysteine, and the position of the binding site for the inhibitor nitrate [Boyington97].

Expression of fdhF is induced by formate and the absence of external electron acceptors, and is repressed by nitrate, nitrite, trimethylamine N-oxide, and oxygen [Wu87, Pecher83, Abaibou97]. Formate can overcome repression by nitrate but not by oxygen [Pecher83].

Inhibition of DNA gyrase enhances expression of fdhF [Axley88].

Locations: periplasmic space, cytosol, membrane

Map Position: [4,295,242 <- 4,297,389]

Molecular Weight of Polypeptide: 79.374 kD (from nucleotide sequence), 80 kD (experimental) [Axley90 ]

pI: 6.1 [Blattner93]

Unification Links: ASAP:ABE-0013363 , CGSC:18400 , DIP:DIP-9572N , EchoBASE:EB0281 , EcoGene:EG10285 , EcoliWiki:b4079 , OU-Microarray:b4079 , PortEco:fdhF , PR:PRO_000022580 , Protein Model Portal:P07658 , RefSeq:NP_418503 , RegulonDB:EG10285 , SMR:P07658 , String:511145.b4079 , UniProt:P07658

Relationship Links: InterPro:IN-FAMILY:IPR006478 , InterPro:IN-FAMILY:IPR006655 , InterPro:IN-FAMILY:IPR006656 , InterPro:IN-FAMILY:IPR006657 , InterPro:IN-FAMILY:IPR006963 , InterPro:IN-FAMILY:IPR009010 , InterPro:IN-FAMILY:IPR027467 , PDB:Structure:1AA6 , PDB:Structure:1FDI , PDB:Structure:1FDO , PDB:Structure:2IV2 , Pfam:IN-FAMILY:PF00384 , Pfam:IN-FAMILY:PF01568 , Pfam:IN-FAMILY:PF04879 , Prosite:IN-FAMILY:PS00490 , Prosite:IN-FAMILY:PS00551 , Prosite:IN-FAMILY:PS00932 , Prosite:IN-FAMILY:PS51669 , Smart:IN-FAMILY:SM00926

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0015944 - formate oxidation Inferred from experiment [Axley91]
GO:0015942 - formate metabolic process Inferred by computational analysis [GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0030151 - molybdenum ion binding Inferred from experiment Inferred by computational analysis [GOA01a, Axley90]
GO:0051539 - 4 iron, 4 sulfur cluster binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Boyington97]
GO:0008863 - formate dehydrogenase (NAD+) activity Inferred by computational analysis [GOA01, GOA01a]
GO:0009055 - electron carrier activity Inferred by computational analysis [GOA01a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a, Gaudet10]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
GO:0051536 - iron-sulfur cluster binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Cox81]
GO:0016020 - membrane Inferred by computational analysis [Gaudet10]
GO:0030288 - outer membrane-bounded periplasmic space Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism energy metabolism, carbon fermentation
metabolism energy production/transport electron donors

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: formate dehydrogenase

formate + an oxidized hydrogenase 3 <=> CO2 + a reduced hydrogenase 3 + H+

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 favored in the direction shown.

In Pathways: hydrogen production V

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: formate dehydrogenase

EC Number: 1.1.99.33

formate + an oxidized electron acceptor + H+ <=> CO2 + a reduced electron acceptor

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.

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The enzyme can catalyze carbon exchange between formate and CO2 in the absence of other electron-accepting molecules [Axley91] and catalyzes formate oxidation without incorporating oxygen from water [Khangulov98].

Cofactors or Prosthetic Groups: molybdopterin [Axley90], Fe2+ [Axley90]

Inhibitors (Competitive): nitrate [Axley91, Axley90, Comment 1]

Inhibitors (Noncompetitive): azide [Axley91, Axley90, Comment 2]

Inhibitors (Unknown Mechanism): nitrite [Axley90] , oxygen [Axley90] , chloride [Axley90]

Kinetic Parameters:

Substrate
Km (μM)
Citations
formate
26000.0
[Axley91]


Subunit of: formate hydrogenlyase complex

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of formate hydrogenlyase complex = [FdhF][(HycD)(HycC)(HycF)(HycG)(HycB)(HycE)]
         formate dehydrogenase H = FdhF (extended summary available)
         hydrogenase 3 = (HycD)(HycC)(HycF)(HycG)(HycB)(HycE) (extended summary available)
                 hydrogenase 3, membrane subunit = HycD (summary available)
                 hydrogenase 3, membrane subunit = HycC (summary available)
                 formate hydrogenlyase complex iron-sulfur protein = HycF (summary available)
                 hydrogenase 3 and formate hydrogenlyase complex, HycG subunit = HycG (summary available)
                 hydrogenase 3, Fe-S subunit = HycB (summary available)
                 hydrogenase 3, large subunit = HycE (extended summary available)

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: formate hydrogenlyase complex

Synonyms: FHL-complex

formate + H+ <=> CO2 + H2

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 favored in the direction shown.

In Pathways: mixed acid fermentation

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 1 -> 56
[UniProt13]
UniProt: 4Fe-4S Mo/W bis-MGD-type.
Metal-Binding-Site 8
[UniProt12]
UniProt: Iron-sulfur (4Fe-4S).
Metal-Binding-Site 10
[UniProt12]
UniProt: Iron-sulfur (4Fe-4S).
Metal-Binding-Site 11
[UniProt12]
UniProt: Iron-sulfur (4Fe-4S).
Metal-Binding-Site 15
[UniProt12]
UniProt: Iron-sulfur (4Fe-4S).
Sequence-Conflict 19
[Zinoni86, UniProt10a]
Alternate sequence: V; UniProt: (in Ref. 1; AAA23754);
Metal-Binding-Site 42
[UniProt12]
UniProt: Iron-sulfur (4Fe-4S).
Amino-Acid-Sites-That-Bind 44
[UniProt12]
UniProt: Molybdopterin 2.
Active-Site 44
[UniProt12]
UniProt: Electron donor/acceptor.
Protein-Segment 110 -> 112
[UniProt12]
UniProt: Molybdopterin 1 binding; Sequence Annotation Type: region of interest.
Metal-Binding-Site 140
[UniProt13]
UniProt: Molybdenum.
Active-Site 140
[UniProt12]
UniProt: Proton donor/acceptor.
Selenocysteine-site 140
[Boyington97, UniProt11a]
UniProt: Selenocysteine.
Amino-Acid-Site 141
[UniProt12]
UniProt: Important for catalytic activity; Sequence Annotation Type: site.
Protein-Segment 173 -> 180
[UniProt12]
UniProt: Molybdopterin 2 binding; Sequence Annotation Type: region of interest.
Protein-Segment 201 -> 204
[UniProt12]
UniProt: Molybdopterin 2 binding; Sequence Annotation Type: region of interest.
Protein-Segment 221 -> 223
[UniProt12]
UniProt: Molybdopterin 2 binding; Sequence Annotation Type: region of interest.
Amino-Acid-Sites-That-Bind 297
[UniProt12]
UniProt: Molybdopterin 2; via amide nitrogen.
Amino-Acid-Sites-That-Bind 301
[UniProt12]
UniProt: Molybdopterin 1.
Amino-Acid-Site 333
[UniProt12]
UniProt: Important for catalytic activity; Sequence Annotation Type: site.
Amino-Acid-Sites-That-Bind 335
[UniProt12]
UniProt: Molybdopterin 1.
Protein-Segment 402 -> 410
[UniProt12]
UniProt: Molybdopterin 1 binding; Sequence Annotation Type: region of interest.
Protein-Segment 428 -> 429
[UniProt12]
UniProt: Molybdopterin 1 binding; Sequence Annotation Type: region of interest.
Amino-Acid-Sites-That-Bind 445
[UniProt12]
UniProt: Molybdopterin 1.
Amino-Acid-Sites-That-Bind 478
[UniProt12]
UniProt: Molybdopterin 1.
Protein-Segment 579 -> 581
[UniProt12]
UniProt: Molybdopterin 1 binding; Sequence Annotation Type: region of interest.
Protein-Segment 581 -> 587
[UniProt12]
UniProt: Molybdopterin 2 binding; Sequence Annotation Type: region of interest.
Amino-Acid-Sites-That-Bind 588
[UniProt12]
UniProt: Molybdopterin 1; via amide nitrogen.
Amino-Acid-Sites-That-Bind 654
[UniProt12]
UniProt: Molybdopterin 1.
Amino-Acid-Sites-That-Bind 655
[UniProt12]
UniProt: Molybdopterin 2.
Protein-Segment 661 -> 662
[UniProt12]
UniProt: Molybdopterin 1 binding; Sequence Annotation Type: region of interest.
Amino-Acid-Sites-That-Bind 678
[UniProt12]
UniProt: Molybdopterin 1.
Amino-Acid-Sites-That-Bind 679
[UniProt12]
UniProt: Molybdopterin 2.

History:
10/20/97 Gene b4079 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10285; confirmed by SwissProt match.


References

Abaibou97: Abaibou H, Giordano G, Mandrand-Berthelot MA (1997). "Suppression of Escherichia coli formate hydrogenlyase activity by trimethylamine N-oxide is due to drainage of the inducer formate." Microbiology 143 ( Pt 8);2657-64. PMID: 9274019

Axley88: Axley MJ, Stadtman TC (1988). "Anaerobic induction of Escherichia coli formate dehydrogenase (hydrogenase-linked) is enhanced by gyrase inactivation." Proc Natl Acad Sci U S A 85(4);1023-7. PMID: 2829213

Axley90: Axley MJ, Grahame DA, Stadtman TC (1990). "Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component." J Biol Chem 1990;265(30);18213-8. PMID: 2211698

Axley91: Axley MJ, Grahame DA (1991). "Kinetics for formate dehydrogenase of Escherichia coli formate-hydrogenlyase." J Biol Chem 266(21);13731-6. PMID: 1906883

Blattner93: Blattner FR, Burland V, Plunkett G, Sofia HJ, Daniels DL (1993). "Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes." Nucleic Acids Res 1993;21(23);5408-17. PMID: 8265357

Boyington97: Boyington JC, Gladyshev VN, Khangulov SV, Stadtman TC, Sun PD (1997). "Crystal structure of formate dehydrogenase H: catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 cluster." Science 275(5304);1305-8. PMID: 9036855

Cox81: Cox JC, Edwards ES, DeMoss JA (1981). "Resolution of distinct selenium-containing formate dehydrogenases from Escherichia coli." J Bacteriol 145(3);1317-24. PMID: 7009577

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

GEST55: GEST H, PECK HD (1955). "A study of the hydrogenlyase reaction with systems derived from normal and anaerogenic coli-aerogenes bacteria." J Bacteriol 70(3);326-34. PMID: 13263293

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Khangulov98: Khangulov SV, Gladyshev VN, Dismukes GC, Stadtman TC (1998). "Selenium-containing formate dehydrogenase H from Escherichia coli: a molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer." Biochemistry 37(10);3518-28. PMID: 9521673

Pecher83: Pecher A, Zinoni F, Jatisatienr C, Wirth R, Hennecke H, Bock A (1983). "On the redox control of synthesis of anaerobically induced enzymes in enterobacteriaceae." Arch Microbiol 136(2);131-6. PMID: 6360066

Peck57: Peck HD, Gest H (1957). "Formic dehydrogenase and the hydrogenlyase enzyme complex in coli-aerogenes bacteria." J Bacteriol 73(6);706-21. PMID: 13449036

Sauter92: Sauter M, Bohm R, Bock A (1992). "Mutational analysis of the operon (hyc) determining hydrogenase 3 formation in Escherichia coli." Mol Microbiol 1992;6(11);1523-32. PMID: 1625581

Sawers94: Sawers G (1994). "The hydrogenases and formate dehydrogenases of Escherichia coli." Antonie Van Leeuwenhoek 1994;66(1-3);57-88. PMID: 7747941

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

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt12: UniProt Consortium (2012). "UniProt version 2012-09 released on 2012-09-12 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

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

Wu87: Wu LF, Mandrand-Berthelot MA (1987). "Regulation of the fdhF gene encoding the selenopolypeptide for benzyl viologen-linked formate dehydrogenase in Escherichia coli." Mol Gen Genet 209(1);129-34. PMID: 3118141

Zinoni86: Zinoni F, Birkmann A, Stadtman TC, Bock A (1986). "Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogen-lyase-linked) from Escherichia coli." Proc Natl Acad Sci U S A 1986;83(13);4650-4. PMID: 2941757


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13B.