EzCatDB: M00042
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DB codeM00042
RLCP classification10.21022.100.10500 : Electron transfer
10.21022.100.10510 : Electron transfer
10.22022.100.10700 : Electron transfer
10.22022.100.10750 : Electron transfer
10.22120.100.10610 : Electron transfer
CATH domainDomain 13.10.20.30 : Ubiquitin-like (UB roll)Catalytic domain
Domain 21.10.287.430 : Helix HairpinsCatalytic domain
Domain 33.30.70.20 : Alpha-Beta PlaitsCatalytic domain
Domain 43.40.50.1780 : Rossmann foldCatalytic domain
Domain 53.40.950.10 : Fe-only Hydrogenase (Larger Subunit); Chain L, domain 3Catalytic domain
E.C.1.12.7.2

CATH domainRelated DB codes (homologues)
3.10.20.30 : Ubiquitin-like (UB roll)M00039,M00049
3.30.70.20 : Alpha-Beta PlaitsM00207,M00012
3.40.50.1780 : Rossmann foldM00012
3.40.950.10 : Fe-only Hydrogenase (Larger Subunit); Chain L, domain 3M00012

Enzyme Name
UniProtKBKEGG

P29166
Protein nameIron hydrogenase 1ferredoxin hydrogenase
H2 oxidizing hydrogenase
H2 producing hydrogenase [ambiguous]
bidirectional hydrogenase
hydrogen-lyase [ambiguous]
hydrogenase (ferredoxin)
hydrogenase I
hydrogenase II
hydrogenlyase [ambiguous]
uptake hydrogenase [ambiguous]
SynonymsEC 1.12.7.2
[Fe] hydrogenase
Fe-only hydrogenase
CpI
PfamPF02906 (Fe_hyd_lg_C)
PF02256 (Fe_hyd_SSU)
PF13237 (Fer4_10)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00630Glyoxylate and dicarboxylate metabolism
MAP00680Methane metabolism

UniProtKB:Accession NumberP29166
Entry namePHF1_CLOPA
ActivityH(2) + 2 oxidized ferredoxin = 2 reduced ferredoxin + 2 H(+).
SubunitMonomer.
Subcellular location
CofactorBinds 1 2Fe-2S cluster per subunit.,Binds 4 4Fe-4S clusters per subunit.,Binds 2 iron ions per subunit. Besides cysteine ligand the diiron subcluster contains non-protein ligands including 2 sulfur atoms, 1 water and 5 cyanide or carbon monoxide ligands.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idL00023L00024L00029C00138C00080C00282C00139
Compound[2Fe-2S][4Fe-4S][4Fe-4S]--diiron/2S/5CO(H-cluster)Reduced ferredoxinH+H2Oxidized ferredoxin
Typeheavy metal,sulfide groupheavy metal,sulfide groupheavy metal,sulfide groupheavy metal,peptide/protein,sulfide groupothersothersheavy metal,peptide/protein,sulfide group
ChEBI33739
33725


15378
18276

PubChem



1038
783
58838673

               
1c4aA01Bound:FESUnboundUnboundUnbound  Unbound
1c4cA01Bound:FESUnboundUnboundUnbound  Unbound
1fehA01Bound:FESUnboundUnboundUnbound  Unbound
1c4aA02UnboundBound:SF4UnboundUnbound  Unbound
1c4cA02UnboundBound:SF4UnboundUnbound  Unbound
1fehA02UnboundBound:SF4UnboundUnbound  Unbound
1c4aA03UnboundBound:2xSF4UnboundUnbound  Unbound
1c4cA03UnboundBound:2xSF4UnboundUnbound  Unbound
1fehA03UnboundBound:2xSF4UnboundUnbound  Unbound
1c4aA04UnboundUnboundUnboundUnbound  Unbound
1c4cA04UnboundUnboundUnboundUnbound  Unbound
1fehA04UnboundUnboundUnboundUnbound  Unbound
1c4aA05UnboundUnboundBound:SF4-HC1Unbound  Unbound
1c4cA05UnboundUnboundBound:SF4-HC0Unbound  Unbound
1fehA05UnboundUnboundBound:SF4-HC1Unbound  Unbound

Active-site residues
resource
Swiss-prot;P29166 & literature [17], [19]
pdbCatalytic residuesCofactor-binding residues
          
1c4aA01CYS 34
CYS 34;CYS 46;CYS 49;CYS 62(2Fe-2S cluster)
1c4cA01CYS 34
CYS 34;CYS 46;CYS 49;CYS 62(2Fe-2S cluster)
1fehA01CYS 34
CYS 34;CYS 46;CYS 49;CYS 62(2Fe-2S cluster)
1c4aA02HIS 94;CYS 98
HIS 94;CYS 98;CYS 101;CYS 107(4Fe-4S cluster-1)
1c4cA02HIS 94;CYS 98
HIS 94;CYS 98;CYS 101;CYS 107(4Fe-4S cluster-1)
1fehA02HIS 94;CYS 98
HIS 94;CYS 98;CYS 101;CYS 107(4Fe-4S cluster-1)
1c4aA03CYS 147;CYS 150;CYS 153;MET 166;CYS 193;GLN 195;CYS 196;VAL 202
CYS 147;CYS 150;CYS 153;CYS 200(4Fe-4S cluster-2);CYS 157;CYS 190;CYS 193;CYS 196(4Fe-4S cluster-3)
1c4cA03CYS 147;CYS 150;CYS 153;MET 166;CYS 193;GLN 195;CYS 196;VAL 202
CYS 147;CYS 150;CYS 153;CYS 200(4Fe-4S cluster-2);CYS 157;CYS 190;CYS 193;CYS 196(4Fe-4S cluster-3)
1fehA03CYS 147;CYS 150;CYS 153;MET 166;CYS 193;GLN 195;CYS 196;VAL 202
CYS 147;CYS 150;CYS 153;CYS 200(4Fe-4S cluster-2);CYS 157;CYS 190;CYS 193;CYS 196(4Fe-4S cluster-3)
1c4aA04LYS 358
CYS 355(4Fe-4S cluster-4 [H-cluster])
1c4cA04LYS 358
CYS 355(4Fe-4S cluster-4 [H-cluster])
1fehA04LYS 358
CYS 355(4Fe-4S cluster-4 [H-cluster])
1c4aA05CYS 299;CYS 499
CYS 300;CYS 499(4Fe-4S cluster-4 [H-cluster]);CYS 503(4Fe-4S cluster-4 & diiron [2Fe] subcluster [H-cluster])
1c4cA05CYS 299;CYS 499
CYS 300;CYS 499(4Fe-4S cluster-4 [H-cluster]);CYS 503(4Fe-4S cluster-4 & diiron [2Fe] subcluster [H-cluster])
1fehA05CYS 299;CYS 499
CYS 300;CYS 499(4Fe-4S cluster-4 [H-cluster]);CYS 503(4Fe-4S cluster-4 & diiron [2Fe] subcluster [H-cluster])

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]Fig.1
[16]

[17]p.1856-1857
[27]Scheme 1, p.1428
[30]Scheme 3, p.4780
[33]Fig.5, p.926-9306

references
[1]
PubMed ID6331453
JournalBiochem Biophys Res Commun
Year1984
Volume122
Pages9-16
AuthorsChen JS, Blanchard DK
TitlePurification and properties of the H2-oxidizing (uptake) hydrogenase of the N2-fixing anaerobe Clostridium pasteurianum W5.
[2]
PubMed ID6327705
JournalJ Biol Chem
Year1984
Volume259
Pages7045-55
AuthorsAdams MW, Mortenson LE
TitleThe physical and catalytic properties of hydrogenase II of Clostridium pasteurianum. A comparison with hydrogenase I.
[3]
PubMed ID6094552
JournalJ Biol Chem
Year1984
Volume259
Pages14328-31
AuthorsWang G, Benecky MJ, Huynh BH, Cline JF, Adams MW, Mortenson LE, Hoffman BM, Munck E
TitleMossbauer and electron nuclear double resonance study of oxidized bidirectional hydrogenase from Clostridium pasteurianum W5.
[4]
PubMed ID3015247
JournalBiochimie
Year1986
Volume68
Pages35-42
AuthorsAdams MW, Johnson MK, Zambrano IC, Mortenson LE
TitleOn the novel H2-activating iron-sulfur center of the "Fe-only" hydrogenases.
[5]
PubMed ID3025213
JournalJ Biol Chem
Year1987
Volume262
Pages38-41
AuthorsRusnak FM, Adams MW, Mortenson LE, Munck E
TitleMossbauer study of Clostridium pasteurianum hydrogenase II. Evidence for a novel three-iron cluster.
[6]
PubMed ID2655584
JournalBiochem J
Year1989
Volume259
Pages597-600
AuthorsGeorge GN, Prince RC, Stokley KE, Adams MW, Stockley KE
TitleX-ray-absorption-spectroscopic evidence for a novel iron cluster in hydrogenase II from Clostridium pasteurianum.
[7]
PubMed ID2464579
JournalJ Bacteriol
Year1989
Volume171
Pages430-5
AuthorsKovacs KL, Seefeldt LC, Tigyi G, Doyle CM, Mortenson LE, Arp DJ
TitleImmunological relationship among hydrogenases.
[8]
PubMed ID2538440
JournalJ Biol Chem
Year1989
Volume264
Pages4342-8
AuthorsKowal AT, Adams MW, Johnson MK
TitleElectron paramagnetic resonance studies of the low temperature photolytic behavior of oxidized hydrogenase I from Clostridium pasteurianum.
[9]
PubMed ID2556390
JournalJ Biol Chem
Year1989
Volume264
Pages20974-83
AuthorsZambrano IC, Kowal AT, Mortenson LE, Adams MW, Johnson MK
TitleMagnetic circular dichroism and electron paramagnetic resonance studies of hydrogenases I and II from Clostridium pasteurianum.
[10]
PubMed ID2544883
JournalProc Natl Acad Sci U S A
Year1989
Volume86
Pages4932-6
AuthorsAdams MW, Eccleston E, Howard JB
TitleIron-sulfur clusters of hydrogenase I and hydrogenase II of Clostridium pasteurianum.
[11]
PubMed ID2173950
JournalBiochim Biophys Acta
Year1990
Volume1020
Pages115-45
AuthorsAdams MW
TitleThe structure and mechanism of iron-hydrogenases.
[12]
PubMed ID1911757
JournalBiochemistry
Year1991
Volume30
Pages9697-704
AuthorsMeyer J, Gagnon J
TitlePrimary structure of hydrogenase I from Clostridium pasteurianum.
[13]
PubMed ID8490025
JournalBiochemistry
Year1993
Volume32
Pages4813-9
AuthorsFu W, Drozdzewski PM, Morgan TV, Mortenson LE, Juszczak A, Adams MW, He SH, Peck HD Jr, DerVartanian DV, LeGall J, et al
TitleResonance Raman studies of iron-only hydrogenases.
[14]
PubMed ID9843404
JournalBiochemistry
Year1998
Volume37
Pages15974-80
AuthorsAtta M, Lafferty ME, Johnson MK, Gaillard J, Meyer J
TitleHeterologous biosynthesis and characterization of the [2Fe-2S]-containing N-terminal domain of Clostridium pasteurianum hydrogenase.
[15]
PubMed ID9485416
JournalBiochemistry
Year1998
Volume37
Pages2660-5
AuthorsDe Luca G, Asso M, Belaich JP, Dermoun Z
TitlePurification and characterization of the HndA subunit of NADP-reducing hydrogenase from Desulfovibrio fructosovorans overproduced in Escherichia coli.
[16]
PubMed ID9874636
JournalScience
Year1998
Volume282
Pages1842-3
AuthorsAdams MW, Stiefel EI
TitleBiological hydrogen production: not so elementary.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS)
Medline ID99055388
PubMed ID9836629
JournalScience
Year1998
Volume282
Pages1853-8
AuthorsPeters JW, Lanzilotta WN, Lemon BJ, Seefeldt LC
TitleX-ray crystal structure of the Fe-only hydrogenase (CpI) from Clostridium pasteurianum to 1.8 angstrom resolution.
Related PDB1feh
Related UniProtKBP29166
[18]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID99459241
PubMed ID10529166
JournalBiochemistry
Year1999
Volume38
Pages12969-73
AuthorsLemon BJ, Peters JW
TitleBinding of exogenously added carbon monoxide at the active site of the iron-only hydrogenase (CpI) from Clostridium pasteurianum.
Related PDB1c4a,1c4c
Related UniProtKBP29166
[19]
PubMed ID10607666
JournalCurr Opin Struct Biol
Year1999
Volume9
Pages670-6
AuthorsPeters JW
TitleStructure and mechanism of iron-only hydrogenases.
[20]
PubMed ID9930693
JournalNature
Year1999
Volume397
Pages214-5
AuthorsCammack R
TitleHydrogenase sophistication.
[21]
PubMed ID10858294
JournalBiochemistry
Year2000
Volume39
Pages7455-60
AuthorsBennett B, Lemon BJ, Peters JW
TitleReversible carbon monoxide binding and inhibition at the active site of the Fe-only hydrogenase.
[22]
PubMed ID10694885
JournalTrends Biochem Sci
Year2000
Volume25
Pages138-43
AuthorsNicolet Y, Lemon BJ, Fontecilla-Camps JC, Peters JW
TitleA novel FeS cluster in Fe-only hydrogenases.
[23]
PubMed ID11457119
JournalJ Am Chem Soc
Year2001
Volume123
Pages3828-9
AuthorsFan HJ, Hall MB
TitleA capable bridging ligand for Fe-only hydrogenase: density functional calculations of a low-energy route for heterolytic cleavage and formation of dihydrogen.
[24]
PubMed ID11457062
JournalJ Am Chem Soc
Year2001
Volume123
Pages3268-78
AuthorsLyon EJ, Georgakaki IP, Reibenspies JH, Darensbourg MY
TitleCoordination sphere flexibility of active-site models for Fe-only hydrogenase: studies in intra- and intermolecular diatomic ligand exchange.
[25]
PubMed ID11827551
JournalBiochemistry
Year2002
Volume41
Pages2036-43
AuthorsChen Z, Lemon BJ, Huang S, Swartz DJ, Peters JW, Bagley KA
TitleInfrared studies of the CO-inhibited form of the Fe-only hydrogenase from Clostridium pasteurianum I: examination of its light sensitivity at cryogenic temperatures.
[26]
PubMed ID11921392
JournalChembiochem
Year2002
Volume3
Pages153-60
AuthorsFrey M
TitleHydrogenases: hydrogen-activating enzymes.
[27]
PubMed ID11896710
JournalInorg Chem
Year2002
Volume41
Pages1421-9
AuthorsBruschi M, Fantucci P, De Gioia L
TitleDFT investigation of structural, electronic, and catalytic properties of diiron complexes related to the [2Fe](H) subcluster of Fe-only hydrogenases.
[28]
PubMed ID12121756
JournalJ Inorg Biochem
Year2002
Volume91
Pages1-8
AuthorsNicolet Y, Cavazza C, Fontecilla-Camps JC
TitleFe-only hydrogenases: structure, function and evolution.
[29]
PubMed ID12727516
JournalCurr Opin Struct Biol
Year2003
Volume13
Pages220-6
AuthorsDrennan CL, Peters JW
TitleSurprising cofactors in metalloenzymes.
[30]
PubMed ID12870970
JournalInorg Chem
Year2003
Volume42
Pages4773-81
AuthorsBruschi M, Fantucci P, De Gioia L
TitleDensity functional theory investigation of the active site of [Fe]-hydrogenases: effects of redox state and ligand characteristics on structural, electronic, and reactivity properties of complexes related to the [2Fe]H subcluster.
[31]
PubMed ID12642671
JournalProc Natl Acad Sci U S A
Year2003
Volume100
Pages3683-8
AuthorsDarensbourg MY, Lyon EJ, Zhao X, Georgakaki IP
TitleThe organometallic active site of [Fe]hydrogenase: models and entatic states.
[32]
PubMed ID15062773
JournalCurr Opin Chem Biol
Year2004
Volume8
Pages133-40
AuthorsArmstrong FA
TitleHydrogenases: active site puzzles and progress.
[33]
PubMed ID14753812
JournalInorg Chem
Year2004
Volume43
Pages923-30
AuthorsZhou T, Mo Y, Liu A, Zhou Z, Tsai KR
TitleEnzymatic mechanism of Fe-only hydrogenase: density functional study on H-H making/breaking at the diiron cluster with concerted proton and electron transfers.
[34]
PubMed ID15667253
JournalBiochem Soc Trans
Year2005
Volume33
Pages20-1
AuthorsSundararajan M, McNamara JP, Mohr M, Hillier IH, Wang H
TitleA semi-empirical molecular orbital scheme to study electron transfer in iron-sulphur proteins.
[35]
PubMed ID15762706
JournalInorg Chem
Year2005
Volume44
Pages1794-809
AuthorsFiedler AT, Brunold TC
TitleCombined spectroscopic/computational study of binuclear Fe(I)-Fe(I) complexes: implications for the fully-reduced active-site cluster of Fe-only hydrogenases.
[36]
PubMed ID15703733
JournalNature
Year2005
Volume433
Pages589-91
AuthorsDarensbourg MY
TitleSynthetic chemistry: making a natural fuel cell.
[37]
PubMed ID15703741
JournalNature
Year2005
Volume433
Pages610-3
AuthorsTard C, Liu X, Ibrahim SK, Bruschi M, De Gioia L, Davies SC, Yang X, Wang LS, Sawers G, Pickett CJ
TitleSynthesis of the H-cluster framework of iron-only hydrogenase.

comments
This enzyme belongs to Fe-only hydrogenases. This enzyme is homologous to [Fe] hydrogenase (or DdH) (M00012 in EzCatDB). iomethyl)amine and 5 cyanide or carbon monoxide molecules. Although this enzyme is homologous to DdH (M00012), the direction of electron transfer is opposite to the counpterpart enzyme, DdH (see M00012).
This enzyme binds five cofactors, a 2FE-2S cluster, three 4Fe-4S clusters, and one H cluster. The H cluster is composed of 4Fe-4S cluster, diiron (2Fe) subcluster, bridged via a thiolate of Cys503. The diiron subcluster is liganded by 2 sulfur atoms, 1 water, and 5 cyanide or carbon monoxide molecules.
According to the literature [16], this enzyme catalyzes the following reactions:
(A) Electron transfer from ferredoxin to the 2Fe-2S cluster:
(A') Electron transfer from ferredoxin to the 4Fe-4S cluster-1:
(B) Electron transfer from the 2Fe-2S cluster to the 4Fe-4S cluster-2:
(B') Electron transfer from the 4Fe-4S cluster-1 to the 4Fe-4S cluster-2:
(C) Electron transfer from the 4Fe-4S cluster-2 to the 4Fe-4S cluster-3:
(D) Electron transfer from the 4Fe-4S cluster-3 to the H cluster:
(E) Hydrogenation (H2 production from 2 H+ ions) at H cluster:
The reactions proceeds as follows (see [17]):
(A') Electron transfer from ferredoxin to the 4Fe-4S cluster-1:
(A'1) Indirect transfer from 2Fe-2S of ferredoxin through Cys98 bound to 4Fe-4S cluster-1.
(B) Electron transfer from the 2Fe-2S cluster to the 4Fe-4S cluster-2:
(B1) Indirect transfer from Cys34 bound to 2Fe-2S to Cys150 bound to 4Fe-4S cluster-2.
(B') Electron transfer from the 4Fe-4S cluster-1 to the 4Fe-4S cluster-2:
(B'1) Indirect transfer from His94 bound to 4Fe-4S cluster-1 to either sulfur of the 4Fe-4S cluster-2 or Cys147 through Val202.
(C) Electron transfer from the 4Fe-4S cluster-2 to the 4Fe-4S cluster-3:
(C1) Indirect transfer from Cys153 bound to 4Fe-4S cluster-2 to Cys196 bound to 4Fe-4S cluster-3 (probably through Met166).
(D) Electron transfer from the 4Fe-4S cluster-3 to the H cluster:
(D1) Indirect transfer from Cys193 bound to 4Fe-4S cluster-3 to Cys499 bound to H cluster.

createdupdated
2005-08-112009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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