EzCatDB: M00012

DB codeM00012
RLCP classification10.120022.100.10610
10.22022.100.10751
10.22100.110.10570
CATH domainDomain 13.40.50.1780Catalytic domain
Domain 23.30.70.20
Domain 33.40.950.10Catalytic domain
Domain 44.10.260.20
E.C.1.12.7.2
CSA1hfe
MACiEM0127

CATH domainRelated DB codes (homologues)
3.30.70.20M00207,M00042
3.40.50.1780M00042
3.40.950.10M00042

Enzyme Name
Swiss-protKEGG

P07598P07603
Protein namePeriplasmic [Fe] hydrogenase large subunitPeriplasmic [Fe] hydrogenase small subunitferredoxin 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 hydrogenlyase
EC 1.12.7.2
Fe hydrogenlyase small chain

KEGG pathways
MAP codePathways
MAP00630Glyoxylate and dicarboxylate metabolism
MAP00680Methane metabolism

Swiss-prot:Accession NumberP07598P07603
Entry namePHFL_DESVHPHFS_DESVH
ActivityH(2) + 2 oxidized ferredoxin = 2 reduced ferredoxin + 2 H(+).H(2) + 2 oxidized ferredoxin = 2 reduced ferredoxin + 2 H(+).
SubunitHeterodimer of a large and a small subunit.Heterodimer of a large and a small subunit.
Subcellular locationPeriplasm.Periplasm.
CofactorBinds 3 4Fe-4S clusters per subunit.,Binds 2 iron ions per subunit.


CofactorsSubstratesProducts
KEGG-idL00024L00030C00282C00125C00125C00126C00126C00080
Compound[4Fe-4S][4Fe-4S]--diiron/di(thiomethyl)amine/2CN/2CO(H-cluster)H2Ferricytochrome c3Ferricytochrome c6Ferrocytochrome c3Ferrocytochrome c6H+
Typeheavy metal,sulfide groupheavy metal,sulfide groupothersamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide groupamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide groupamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide groupamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide groupothers
1hfeL01UnboundAnalogue:SF4-2xFE2-2xCYN-2xCMO-PDT
UnboundUnboundUnboundUnbound
1hfeM01UnboundAnalogue:SF4-2xFE2-2xCYN-2xCMO-PDT
UnboundUnboundUnboundUnbound
1e08A01UnboundAnalogue:SF4-2xFE2-2xCYN-2xCMO-PDT
UnboundUnboundUnboundUnbound
1hfeL02Bound:2xSF4Unbound
UnboundUnboundUnboundUnbound
1hfeM02Bound:2xSF4Unbound
UnboundUnboundUnboundUnbound
1e08A02Bound:2xSF4Unbound
UnboundBound:HEM(chain E)UnboundUnbound
1hfeL03UnboundUnbound
UnboundUnboundUnboundUnbound
1hfeM03UnboundUnbound
UnboundUnboundUnboundUnbound
1e08A03UnboundUnbound
UnboundUnboundUnboundUnbound
1hfeSUnboundUnbound
UnboundUnboundUnboundUnbound
1hfeTUnboundUnbound
UnboundUnboundUnboundUnbound
1e08DUnboundUnbound
UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P07598 & literature [8], [10], [12], [15]
pdbCatalytic residuesCofactor-binding residues
1hfeL01LYS 237
CYS 234(4Fe-4S cluster-3 [H-cluster]);CYS 382(4Fe-4S cluster-3 & diiron [2Fe] subcluster binding [H-cluster])
1hfeM01LYS 237
CYS 234(4Fe-4S cluster-3 [H-cluster]);CYS 382(4Fe-4S cluster-3 & diiron [2Fe] subcluster binding [H-cluster])
1e08A01LYS 237
CYS 234(4Fe-4S cluster-3 [H-cluster]);CYS 382(4Fe-4S cluster-3 & diiron [2Fe] subcluster binding [H-cluster])
1hfeL02CYS 38;CYS 41;ILE 50;CYS 69;GLN 71;CYS 72
CYS 35;CYS 38;CYS 41;CYS 76(4Fe-4S cluster-1);CYS 45;CYS 66;CYS 69;CYS 72(4Fe-4S cluster-2)
1hfeM02CYS 38;CYS 41;ILE 50;CYS 69;GLN 71;CYS 72
CYS 35;CYS 38;CYS 41;CYS 76(4Fe-4S cluster-1);CYS 45;CYS 66;CYS 69;CYS 72(4Fe-4S cluster-2)
1e08A02CYS 38;CYS 41;ILE 50;CYS 69;GLN 71;CYS 72
CYS 35;CYS 38;CYS 41;CYS 76(4Fe-4S cluster-1);CYS 45;CYS 66;CYS 69;CYS 72(4Fe-4S cluster-2)
1hfeL03CYS 178;CYS 378
CYS 179;CYS 378(4Fe-4S cluster-3 [H-cluster])
1hfeM03CYS 178;CYS 378
CYS 179;CYS 378(4Fe-4S cluster-3 [H-cluster])
1e08A03CYS 178;CYS 378
CYS 179;CYS 378(4Fe-4S cluster-3 [H-cluster])
1hfeS

1hfeT

1e08D


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.12, Fig.13, Fig.14, p.137-138, p.139-140
[8]p.16-20
[9]Fig.1
[10]p.672-674
[11]

[12]p.141-142
[13]

[16]Fig.2, p.154-157
[17]Scheme 1, p.1428-1429
[18]p.2-4
[19]

[20]

[23]Scheme 1, Scheme 2, Scheme 3, p.4778-4781
[26]Fig.5, p.926-9306

references
[1]
PubMed ID2830138
JournalFEBS Lett
Year1988
Volume228
Pages85-8
AuthorsPatil DS, He SH, DerVartanian DV, Le Gall J, Huynh BH, Peck HD Jr
TitleThe relationship between activity and the axial g = 2.06 EPR signal induced by CO in the periplasmic (Fe) hydrogenase from Desulfovibrio vulgaris.
[2]
PubMed ID2848804
JournalJ Biol Chem
Year1988
Volume263
Pages18732-8
AuthorsPatil DS, Moura JJ, He SH, Teixeira M, Prickril BC, DerVartanian DV, Peck HD Jr, LeGall J, Huynh BH
TitleEPR-detectable redox centers of the periplasmic hydrogenase from Desulfovibrio vulgaris.
[3]
PubMed ID2173950
JournalBiochim Biophys Acta
Year1990
Volume1020
Pages115-45
AuthorsAdams MW
TitleThe structure and mechanism of iron-hydrogenases.
[4]
PubMed ID1327776
JournalEur J Biochem
Year1992
Volume209
Pages357-65
AuthorsHatchikian EC, Forget N, Fernandez VM, Williams R, Cammack R
TitleFurther characterization of the [Fe]-hydrogenase from Desulfovibrio desulfuricans ATCC 7757.
[5]
PubMed ID8198565
JournalBiochem Biophys Res Commun
Year1994
Volume201
Pages128-34
AuthorsMus-Veteau I, Guerlesquin F
TitleInvolvement of histidine residues in the catalytic mechanism of hydrogenases.
[6]
PubMed ID9346288
JournalEur J Biochem
Year1997
Volume248
Pages355-61
Authorsvan Dam PJ, Reijerse EJ, Hagen WR
TitleIdentification of a putative histidine base and of a non-protein nitrogen ligand in the active site of Fe-hydrogenases by one-dimensional and two-dimensional electron spin-echo envelope-modulation spectroscopy.
[7]
PubMed ID9849942
JournalProteins
Year1998
Volume33
Pages590-600
AuthorsBrugna M, Giudici-Orticoni MT, Spinelli S, Brown K, Tegoni M, Bruschi M
TitleKinetics and interaction studies between cytochrome c3 and Fe-only hydrogenase from Desulfovibrio vulgaris Hildenborough.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
PubMed ID10368269
JournalStructure Fold Des
Year1999
Volume7
Pages13-23
AuthorsNicolet Y, Piras C, Legrand P, Hatchikian CE, Fontecilla-Camps JC
TitleDesulfovibrio desulfuricans iron hydrogenase: the structure shows unusual coordination to an active site Fe binuclear center.
Related PDB1hfe
Related Swiss-protP07598,P07603
[9]
PubMed ID9930693
JournalNature
Year1999
Volume397
Pages214-5
AuthorsCammack R
TitleHydrogenase sophistication.
[10]
PubMed ID10607666
JournalCurr Opin Struct Biol
Year1999
Volume9
Pages670-6
AuthorsPeters JW
TitleStructure and mechanism of iron-only hydrogenases.
[11]
PubMed ID10748163
JournalJ Biol Chem
Year2000
Volume275
Pages23204-10
AuthorsMorelli X, Czjzek M, Hatchikian CE, Bornet O, Fontecilla-Camps JC, Palma NP, Moura JJ, Guerlesquin F
TitleStructural model of the Fe-hydrogenase/cytochrome c553 complex combining transverse relaxation-optimized spectroscopy experiments and soft docking calculations.
Related PDB1e08
[12]
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.
[13]
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.
[14]
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.
[15]
CommentsX-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS), ABSORPTION, EPR, AND FOURIER-TRANSFORM INFRARED SPECTROSCOPY.
PubMed ID11456758
JournalJ Am Chem Soc
Year2001
Volume123
Pages1596-601
AuthorsNicolet Y, de Lacey AL, Vernede X, Fernandez VM, Hatchikian EC, Fontecilla-Camps JC
TitleCrystallographic and FTIR spectroscopic evidence of changes in Fe coordination upon reduction of the active site of the Fe-only hydrogenase from Desulfovibrio desulfuricans.
Related Swiss-protP07598
[16]
PubMed ID11921392
JournalChembiochem
Year2002
Volume3
Pages153-60
AuthorsFrey M
TitleHydrogenases: hydrogen-activating enzymes.
[17]
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.
[18]
PubMed ID12121756
JournalJ Inorg Biochem
Year2002
Volume91
Pages1-8
AuthorsNicolet Y, Cavazza C, Fontecilla-Camps JC
TitleFe-only hydrogenases: structure, function and evolution.
[19]
PubMed ID[PubMed
JournalJ Chem Phys
Year2002
Volume117
Pages8177-80
AuthorsLiu ZP, Hu P
TitleMechanism of H2 metabolism on Fe-only hydrogenases.
[20]
PubMed ID11982382
Journalcharacterization and electronic structure of the redox states
Year
Volume
Pages
AuthorsLiu ZP, Hu P
TitleA density functional theory study on the active center of Fe-only hydrogenase:
[21]
PubMed ID12727516
JournalCurr Opin Struct Biol
Year2003
Volume13
Pages220-6
AuthorsDrennan CL, Peters JW
TitleSurprising cofactors in metalloenzymes.
[22]
PubMed ID12885397
JournalFEBS Lett
Year2003
Volume548
Pages1-4
AuthorsElAntak L, Morelli X, Bornet O, Hatchikian C, Czjzek M, Dolla A, Guerlesquin F
TitleThe cytochrome c3-[Fe]-hydrogenase electron-transfer complex: structural model by NMR restrained docking.
[23]
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.
[24]
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.
[25]
PubMed ID15062773
JournalCurr Opin Chem Biol
Year2004
Volume8
Pages133-40
AuthorsArmstrong FA
TitleHydrogenases: active site puzzles and progress.
[26]
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.
[27]
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.
[28]
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.
[29]
PubMed ID15703733
JournalNature
Year2005
Volume433
Pages589-91
AuthorsDarensbourg MY
TitleSynthetic chemistry: making a natural fuel cell.
[30]
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 1 (or CpI) (M00042 in EzCatDB).
This enzyme binds three cofactors, two 4Fe-4S clusters, and one H cluster. The H cluster is composed of 4Fe-4S cluster, diiron (2Fe) subcluster, bridged via a thiolate of Cys328. The diiron subcluster is liganded by di(thiomethyl)amine and 5 cyanide or carbon monoxide molecules.
Although this enzyme is homologous to CpI (M00042), the direction of electron transfer is opposite to the counpterpart enzyme, CpI (see [12]), and the electron transport protein, which should accept electrons from this enzyme, is either cytochrome c3 or cytochrome c6, instead of ferredoxin (see [8]).
Cytochrome c proteins bind heme groups, which are covalently bound to the protein themselves through cysteine residues and vinyl groups of the heme groups. Cytochrome c3 binds 4 heme groups(cf. PDB;1a2i), whereas cytochrome c6 binds only a single heme group (cf. PDB;1c6r). In the both of the cytochrome c proteins, the cysteine residues covalently bound to heme groups are exposed to the surface of the proteins.
According to the literature [8], [9], [11] and [12], this enzyme catalyzes the following reactions:
(A) Hydrogenation (H2 oxidation to 2 H+ ions) at H cluster:
(B) Electron transfer from the H cluster to the 4Fe-4S cluster-2:
(D1) Indirect transfer from Cys378 bound to H cluster to Cys69 bound to 4Fe-4S cluster-2 (probably through Gln71).
(C) Electron transfer from the 4Fe-4S cluster-2 to the 4Fe-4S cluster-1:
(C1) Indirect transfer from Cys72 bound to 4Fe-4S cluster-2 to Cys41 bound to 4Fe-4S cluster-1 (probably through Ile50).
(D) Electron transfer from the 4Fe-4S cluster-1 to cytochrome c3 (or c6):
(D1) Indirect transfer from Cys38 (of large subunit) bound to 4Fe-4S cluster-1 to the heme group of cytochrome c through cysteine residue covalently bonded to heme group, and vinyl group of the heme (see [11]).

createdupdated
2005-08-102009-02-26


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 2010)
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)

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