MET8_YEAST
ID MET8_YEAST Reviewed; 274 AA.
AC P15807; D6VQK9;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Siroheme biosynthesis protein MET8 {ECO:0000303|PubMed:10051442};
DE Includes:
DE RecName: Full=Precorrin-2 dehydrogenase {ECO:0000303|PubMed:11980703};
DE EC=1.3.1.76 {ECO:0000269|PubMed:11980703};
DE Includes:
DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000303|PubMed:11980703};
DE EC=4.99.1.4 {ECO:0000269|PubMed:11980703};
GN Name=MET8 {ECO:0000303|PubMed:2408020}; OrderedLocusNames=YBR213W;
GN ORFNames=YBR1461;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 26786 / X2180-1A;
RX PubMed=2408020; DOI=10.1093/nar/18.3.659;
RA Cherest H., Thomas D., Surdin-Kerjan Y.;
RT "Nucleotide sequence of the MET8 gene of Saccharomyces cerevisiae.";
RL Nucleic Acids Res. 18:659-659(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=10051442; DOI=10.1042/bj3380701;
RA Raux E., McVeigh T., Peters S.E., Leustek T., Warren M.J.;
RT "The role of Saccharomyces cerevisiae Met1p and Met8p in sirohaem and
RT cobalamin biosynthesis.";
RL Biochem. J. 338:701-708(1999).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 11-274 IN COMPLEX WITH NAD,
RP SUBUNIT, MUTAGENESIS OF GLY-22; ASP-141 AND HIS-237, AND CATALYTIC
RP ACTIVITY.
RX PubMed=11980703; DOI=10.1093/emboj/21.9.2068;
RA Schubert H.L., Raux E., Brindley A.A., Leech H.K., Wilson K.S., Hill C.P.,
RA Warren M.J.;
RT "The structure of Saccharomyces cerevisiae Met8p, a bifunctional
RT dehydrogenase and ferrochelatase.";
RL EMBO J. 21:2068-2075(2002).
CC -!- FUNCTION: Catalyzes the conversion of precorrin-2 into siroheme. This
CC reaction consist of the NAD-dependent oxidation of precorrin-2 into
CC sirohydrochlorin and its subsequent ferrochelation into siroheme.
CC {ECO:0000269|PubMed:10051442}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + precorrin-2 = 2 H(+) + NADH + sirohydrochlorin;
CC Xref=Rhea:RHEA:15613, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58351, ChEBI:CHEBI:58827; EC=1.3.1.76;
CC Evidence={ECO:0000269|PubMed:11980703};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15614;
CC Evidence={ECO:0000269|PubMed:11980703};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + siroheme = Fe(2+) + sirohydrochlorin;
CC Xref=Rhea:RHEA:24360, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:58351, ChEBI:CHEBI:60052; EC=4.99.1.4;
CC Evidence={ECO:0000269|PubMed:11980703};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24361;
CC Evidence={ECO:0000269|PubMed:11980703};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; siroheme from sirohydrochlorin: step 1/1.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11980703}.
CC -!- SIMILARITY: Belongs to the precorrin-2 dehydrogenase / sirohydrochlorin
CC ferrochelatase family. MET8 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X17271; CAA35173.1; -; Genomic_DNA.
DR EMBL; Z36082; CAA85177.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07329.1; -; Genomic_DNA.
DR PIR; S20155; S20155.
DR RefSeq; NP_009772.1; NM_001178561.1.
DR PDB; 1KYQ; X-ray; 2.20 A; A/B/C=1-274.
DR PDBsum; 1KYQ; -.
DR AlphaFoldDB; P15807; -.
DR SMR; P15807; -.
DR BioGRID; 32910; 112.
DR DIP; DIP-4944N; -.
DR IntAct; P15807; 2.
DR MINT; P15807; -.
DR STRING; 4932.YBR213W; -.
DR iPTMnet; P15807; -.
DR MaxQB; P15807; -.
DR PaxDb; P15807; -.
DR PRIDE; P15807; -.
DR EnsemblFungi; YBR213W_mRNA; YBR213W; YBR213W.
DR GeneID; 852514; -.
DR KEGG; sce:YBR213W; -.
DR SGD; S000000417; MET8.
DR VEuPathDB; FungiDB:YBR213W; -.
DR eggNOG; ENOG502RYIW; Eukaryota.
DR HOGENOM; CLU_011276_8_5_1; -.
DR InParanoid; P15807; -.
DR OMA; KYRMEWI; -.
DR BioCyc; MetaCyc:G3O-29150-MON; -.
DR BioCyc; YEAST:G3O-29150-MON; -.
DR BRENDA; 1.3.1.76; 984.
DR BRENDA; 4.99.1.4; 984.
DR UniPathway; UPA00262; UER00222.
DR UniPathway; UPA00262; UER00376.
DR EvolutionaryTrace; P15807; -.
DR PRO; PR:P15807; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P15807; protein.
DR GO; GO:0004325; F:ferrochelatase activity; IDA:SGD.
DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IDA:SGD.
DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC.
DR GO; GO:0019354; P:siroheme biosynthetic process; IMP:SGD.
DR GO; GO:0000103; P:sulfate assimilation; IMP:SGD.
DR InterPro; IPR028161; Met8.
DR InterPro; IPR028162; Met8_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR028281; Sirohaem_synthase_central.
DR PANTHER; PTHR35330; PTHR35330; 1.
DR Pfam; PF14823; Sirohm_synth_C; 1.
DR Pfam; PF14824; Sirohm_synth_M; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lyase; Multifunctional enzyme; NAD; Oxidoreductase;
KW Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1..274
FT /note="Siroheme biosynthesis protein MET8"
FT /id="PRO_0000096446"
FT ACT_SITE 141
FT /note="Proton acceptor"
FT /evidence="ECO:0000255"
FT BINDING 23..24
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11980703"
FT BINDING 43..45
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11980703"
FT BINDING 93
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11980703"
FT MUTAGEN 22
FT /note="G->D: Loss of dehydrogenase activity. No effect on
FT chelatase activity."
FT /evidence="ECO:0000269|PubMed:11980703"
FT MUTAGEN 141
FT /note="D->A: Loss of chelatase and dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:11980703"
FT MUTAGEN 237
FT /note="H->A: No effect on dehydrogenase or chelatase
FT activity."
FT /evidence="ECO:0000269|PubMed:11980703"
FT CONFLICT 15
FT /note="K -> R (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="I -> M (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="E -> K (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="D -> N (in Ref. 5)"
FT /evidence="ECO:0000305"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 23..32
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:1KYQ"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 117..131
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 135..139
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:1KYQ"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:1KYQ"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 171..188
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 193..210
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 217..235
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 241..252
FT /evidence="ECO:0007829|PDB:1KYQ"
FT TURN 253..256
FT /evidence="ECO:0007829|PDB:1KYQ"
FT HELIX 264..270
FT /evidence="ECO:0007829|PDB:1KYQ"
SQ SEQUENCE 274 AA; 31918 MW; 0EE9A6DE8A43673E CRC64;
MVKSLQLAHQ LKDKKILLIG GGEVGLTRLY KLIPTGCKLT LVSPDLHKSI IPKFGKFIQN
EDQPDYREDA KRFINPNWDP TKNEIYEYIR SDFKDEYLDL EDENDAWYII MTCIPDHPES
ARIYHLCKER FGKQQLVNVA DKPDLCDFYF GANLEIGDRL QILISTNGLS PRFGALVRDE
IRNLFTQMGD LALEDAVVKL GELRRGIRLL APDDKDVKYR MDWARRCTDL FGIQHCHNID
VKRLLDLFKV MFQEQNCSLQ FPPRERLLSE YCSS
