ID   FDHA_METFO              Reviewed;         684 AA.
AC   P06131;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   02-SEP-2026, entry version 113.
DE   RecName: Full=F420-dependent formate dehydrogenase subunit alpha {ECO:0000305};
DE            EC=1.17.98.3 {ECO:0000269|PubMed:2661536, ECO:0000269|PubMed:3801411, ECO:0000269|PubMed:3944055, ECO:0000269|PubMed:6874636, ECO:0000269|PubMed:7061389};
GN   Name=fdhA {ECO:0000303|PubMed:3531194};
OS   Methanobacterium formicicum.
OC   Archaea; Methanobacteriati; Methanobacteriota; Methanomada group;
OC   Methanobacteria; Methanobacteriales; Methanobacteriaceae; Methanobacterium.
OX   NCBI_TaxID=2162;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-26, AND SUBUNIT.
RC   STRAIN=JF-1;
RX   PubMed=3531194; DOI=10.1016/s0021-9258(18)69253-1;
RA   Shuber A.P., Orr E.C., Recny M.A., Schendel P.F., May H.D., Schauer N.L.,
RA   Ferry J.G.;
RT   "Cloning, expression, and nucleotide sequence of the formate dehydrogenase
RT   genes from Methanobacterium formicicum.";
RL   J. Biol. Chem. 261:12942-12947(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RC   STRAIN=JF-1;
RX   PubMed=1378430; DOI=10.1128/jb.174.15.4997-5004.1992;
RA   White W.B., Ferry J.G.;
RT   "Identification of formate dehydrogenase-specific mRNA species and
RT   nucleotide sequence of the fdhC gene of Methanobacterium formicicum.";
RL   J. Bacteriol. 174:4997-5004(1992).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RC   STRAIN=JF-1;
RX   PubMed=7061389; DOI=10.1128/jb.150.1.1-7.1982;
RA   Schauer N.L., Ferry J.G.;
RT   "Properties of formate dehydrogenase in Methanobacterium formicicum.";
RL   J. Bacteriol. 150:1-7(1982).
RN   [4]
RP   ERRATUM OF PUBMED:7061389.
RX   DOI=10.1128/jb.151.3.1642-1642.1982;
RA   Schauer N.L., Ferry J.G.;
RL   J. Bacteriol. 151:1642-1642(1982).
RN   [5]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=6874636; DOI=10.1128/jb.155.2.467-472.1983;
RA   Schauer N.L., Ferry J.G.;
RT   "FAD requirement for the reduction of coenzyme F420 by formate
RT   dehydrogenase from Methanobacterium formicicum.";
RL   J. Bacteriol. 155:467-472(1983).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=3801411; DOI=10.1021/bi00370a059;
RA   Schauer N.L., Ferry J.G., Honek J.F., Orme-Johnson W.H., Walsh C.;
RT   "Mechanistic studies of the coenzyme F420 reducing formate dehydrogenase
RT   from Methanobacterium formicicum.";
RL   Biochemistry 25:7163-7168(1986).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT.
RC   STRAIN=JF-1;
RX   PubMed=3944055; DOI=10.1128/jb.165.2.405-411.1986;
RA   Schauer N.L., Ferry J.G.;
RT   "Composition of the coenzyme F420-dependent formate dehydrogenase from
RT   Methanobacterium formicicum.";
RL   J. Bacteriol. 165:405-411(1986).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=2661536; DOI=10.1128/jb.171.7.3854-3859.1989;
RA   Baron S.F., Ferry J.G.;
RT   "Reconstitution and properties of a coenzyme F420-mediated formate
RT   hydrogenlyase system in Methanobacterium formicicum.";
RL   J. Bacteriol. 171:3854-3859(1989).
RN   [9]
RP   ERRATUM OF PUBMED:2661536.
RA   Baron S.F., Ferry J.G.;
RL   J. Bacteriol. 171:5237-5237(1989).
CC   -!- FUNCTION: Catalyzes the oxidation of formate to carbon dioxide, with
CC       coenzyme F420 as the electron acceptor (PubMed:2661536, PubMed:3801411,
CC       PubMed:3944055, PubMed:6874636, PubMed:7061389). In vitro can also use
CC       methyl viologen, 7,8-didemethyl-8-hydroxy-5-deazariboflavin (or FO, a
CC       hydrolytic derivative of coenzyme F420), FMN and FAD as electron
CC       acceptors, but not NAD(+) or NADP(+) (PubMed:2661536, PubMed:3944055,
CC       PubMed:6874636, PubMed:7061389). {ECO:0000269|PubMed:2661536,
CC       ECO:0000269|PubMed:3801411, ECO:0000269|PubMed:3944055,
CC       ECO:0000269|PubMed:6874636, ECO:0000269|PubMed:7061389}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=oxidized coenzyme F420-(gamma-L-Glu)(n) + formate + 2 H(+) =
CC         reduced coenzyme F420-(gamma-L-Glu)(n) + CO2; Xref=Rhea:RHEA:42764,
CC         Rhea:RHEA-COMP:12939, Rhea:RHEA-COMP:14378, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15740, ChEBI:CHEBI:16526, ChEBI:CHEBI:133980,
CC         ChEBI:CHEBI:139511; EC=1.17.98.3;
CC         Evidence={ECO:0000269|PubMed:2661536, ECO:0000269|PubMed:3801411,
CC         ECO:0000269|PubMed:3944055, ECO:0000269|PubMed:6874636,
CC         ECO:0000269|PubMed:7061389};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250|UniProtKB:P07658};
CC       Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:P07658};
CC   -!- COFACTOR:
CC       Name=Mo-bis(molybdopterin guanine dinucleotide);
CC         Xref=ChEBI:CHEBI:60539; Evidence={ECO:0000269|PubMed:3944055};
CC       Note=Binds 1 molybdenum-bis(molybdopterin guanine dinucleotide) (Mo-
CC       bis-MGD) cofactor per subunit. {ECO:0000269|PubMed:3944055};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:3944055};
CC   -!- ACTIVITY REGULATION: Is extremely sensitive to oxygen (PubMed:7061389).
CC       Strongly inhibited by cyanide, azide, alpha,alpha-dipyridyl and 1,10-
CC       phenanthroline (PubMed:7061389). {ECO:0000269|PubMed:7061389}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6 uM for coenzyme F420 {ECO:0000269|PubMed:7061389};
CC         KM=63 uM for 7,8-didemethyl-8-hydroxy-5-deazariboflavin
CC         {ECO:0000269|PubMed:7061389};
CC         KM=44 uM for FMN {ECO:0000269|PubMed:7061389};
CC         KM=98 uM for FAD {ECO:0000269|PubMed:7061389};
CC         KM=12 uM for protioformate {ECO:0000269|PubMed:3801411};
CC         KM=9 uM for deuterioformate {ECO:0000269|PubMed:3801411};
CC         Vmax=17.4 umol/min/mg enzyme (with coenzyme F420 as electron
CC         acceptor) {ECO:0000269|PubMed:7061389};
CC         Vmax=18.8 umol/min/mg enzyme (with
CC         7,8-didemethyl-8-hydroxy-5-deazariboflavin as electron acceptor)
CC         {ECO:0000269|PubMed:7061389};
CC         Vmax=19.5 umol/min/mg enzyme (with FMN as electron acceptor)
CC         {ECO:0000269|PubMed:7061389};
CC         Vmax=26.6 umol/min/mg enzyme (with FAD as electron acceptor)
CC         {ECO:0000269|PubMed:7061389};
CC       pH dependence:
CC         Optimum pH is 7.9 (when assayed with coenzyme F420).
CC         {ECO:0000269|PubMed:7061389};
CC       Temperature dependence:
CC         Optimum temperature is 55 degrees Celsius.
CC         {ECO:0000269|PubMed:7061389};
CC   -!- SUBUNIT: Dimer of an alpha (FdhA) and a beta (FdhB) subunit.
CC       {ECO:0000269|PubMed:3531194, ECO:0000269|PubMed:3944055}.
CC   -!- SIMILARITY: Belongs to the prokaryotic molybdopterin-containing
CC       oxidoreductase family. {ECO:0000305}.
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DR   EMBL; J02581; AAA72182.1; -; Genomic_DNA.
DR   PIR; A24698; A24698.
DR   RefSeq; WP_048072979.1; NZ_CP006933.1.
DR   AlphaFoldDB; P06131; -.
DR   SMR; P06131; -.
DR   STRING; 2162.BRM9_0168; -.
DR   GeneID; 26738401; -.
DR   OrthoDB; 23466at2157; -.
DR   SABIO-RK; P06131; -.
DR   GO; GO:0016020; C:membrane; IEA:TreeGrafter.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:InterPro.
DR   GO; GO:0043794; F:formate dehydrogenase (coenzyme F420) activity; IDA:MENGO.
DR   GO; GO:0008863; F:formate dehydrogenase (NAD+) activity; IEA:InterPro.
DR   GO; GO:0043546; F:molybdopterin cofactor binding; IEA:InterPro.
DR   GO; GO:0003954; F:NADH dehydrogenase activity; IEA:TreeGrafter.
DR   GO; GO:0015942; P:formate metabolic process; IEA:InterPro.
DR   GO; GO:0022904; P:respiratory electron transport chain; IEA:TreeGrafter.
DR   CDD; cd02790; MopB_CT_Formate-Dh_H; 1.
DR   CDD; cd02753; MopB_Formate-Dh-H; 1.
DR   FunFam; 2.20.25.90:FF:000006; Formate dehydrogenase alpha subunit; 1.
DR   FunFam; 3.40.228.10:FF:000002; Formate dehydrogenase subunit alpha; 1.
DR   FunFam; 2.40.40.20:FF:000005; Periplasmic nitrate reductase; 1.
DR   Gene3D; 2.40.40.20; -; 1.
DR   Gene3D; 3.40.50.740; -; 1.
DR   Gene3D; 2.20.25.90; ADC-like domains; 1.
DR   Gene3D; 3.40.228.10; Dimethylsulfoxide Reductase, domain 2; 1.
DR   InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR   InterPro; IPR041925; CT_Formate-Dh_H.
DR   InterPro; IPR041924; Formate_Dh-H_N.
DR   InterPro; IPR006478; Formate_DH_asu.
DR   InterPro; IPR006657; MoPterin_dinucl-bd_dom.
DR   InterPro; IPR006656; Mopterin_OxRdtase.
DR   InterPro; IPR006963; Mopterin_OxRdtase_4Fe-4S_dom.
DR   InterPro; IPR006655; Mopterin_OxRdtase_prok_CS.
DR   InterPro; IPR027467; MopterinOxRdtase_cofactor_BS.
DR   NCBIfam; TIGR01591; Fdh-alpha; 1.
DR   PANTHER; PTHR43105:SF14; FORMATE DEHYDROGENASE H; 1.
DR   PANTHER; PTHR43105; RESPIRATORY NITRATE REDUCTASE; 1.
DR   Pfam; PF04879; Molybdop_Fe4S4; 1.
DR   Pfam; PF00384; Molybdopterin; 1.
DR   Pfam; PF01568; Molydop_binding; 1.
DR   SMART; SM00926; Molybdop_Fe4S4; 1.
DR   SUPFAM; SSF50692; ADC-like; 1.
DR   SUPFAM; SSF53706; Formate dehydrogenase/DMSO reductase, domains 1-3; 1.
DR   PROSITE; PS51669; 4FE4S_MOW_BIS_MGD; 1.
DR   PROSITE; PS00551; MOLYBDOPTERIN_PROK_1; 1.
DR   PROSITE; PS00490; MOLYBDOPTERIN_PROK_2; 1.
DR   PROSITE; PS00932; MOLYBDOPTERIN_PROK_3; 1.
PE   1: Evidence at protein level;
KW   4Fe-4S; Direct protein sequencing; Iron; Iron-sulfur; Metal-binding;
KW   Molybdenum; Oxidoreductase; Zinc.
FT   CHAIN           1..684
FT                   /note="F420-dependent formate dehydrogenase subunit alpha"
FT                   /id="PRO_0000063225"
FT   DOMAIN          3..59
FT                   /note="4Fe-4S Mo/W bis-MGD-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT   BINDING         10
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT   BINDING         13
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT   BINDING         17
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT   BINDING         45
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
SQ   SEQUENCE   684 AA;  75717 MW;  38D37CF86BFF06E2 CRC64;
     MDIKYVPTIC PYCGVGCGMN LVVKDEKVVG VEPWKRHPVN EGKLCPKGNF CYEIIHREDR
     LTTPLIKENG EFREATWDEA YDLIASKLGA YDPNEIGFFC CARSPNENIY VNQKFARIVV
     GTHNIDHCAR LCHGPTVAGL AASFGSGAMT NSYASFEDAD LIFSIGANSL EAHPLVGRKL
     MRAKMNGAYF IVADPRYTPT AKQADQYIPF KTGTDVALMN AMMNVIISEG LEDKEFIEKR
     TKNYEELKEV VSKYTPEMAE EITQVPADVI RDIAIKYAKA DKAAIVYSLG ITEHSHGVDN
     VMQTANLAML TGNIGRLGTG VNPLRGQNNV QGACDMGALP TDYPGYRKVA DQEVMEDVTC
     TWGCSDLGCE PGLKIPEMID AAAKGDLKVL YITGEDPVIS DPDTHHVEEA LNNLDFFVVQ
     DIFMTDTAEF ADVVLPAACW AEQEGTFTNG ERRVQLIRKA VDAPGESKYD WEIFCDLAKK
     MGADPEMFTY ESAQDIFEEV RTVTPQYAGM NRERLDRPEA LHWPCPSEDH PGTAMMHIEK
     FAHPDGLGIF MPLEEQGPME TPDDEYPLIL TTTRLLFHYH AAMTRRAATL DREVPTGYVE
     INTEDAAELG IANKEKVKVK SRRGEIEIAA RVTDDIVKGI VNIPMHFREC SANILTNAAA
     IDPKSGMPEY KACAVAISKM EGSK
//