ID   A5WD09_PSYWF            Unreviewed;      1272 AA.
AC   A5WD09;
DT   10-JUL-2007, integrated into UniProtKB/TrEMBL.
DT   10-JUL-2007, sequence version 1.
DT   27-MAR-2024, entry version 118.
DE   RecName: Full=Methionine synthase {ECO:0000256|ARBA:ARBA00013998, ECO:0000256|PIRNR:PIRNR000381};
DE            EC=2.1.1.13 {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|PIRNR:PIRNR000381};
DE   AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|ARBA:ARBA00031040, ECO:0000256|PIRNR:PIRNR000381};
GN   OrderedLocusNames=PsycPRwf_0595 {ECO:0000313|EMBL:ABQ93550.1};
OS   Psychrobacter sp. (strain PRwf-1).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Moraxellales; Moraxellaceae;
OC   Psychrobacter.
OX   NCBI_TaxID=349106 {ECO:0000313|EMBL:ABQ93550.1};
RN   [1] {ECO:0000313|EMBL:ABQ93550.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=PRwf-1 {ECO:0000313|EMBL:ABQ93550.1};
RG   US DOE Joint Genome Institute;
RA   Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA   Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA   Chain P., Malfatti S., Shin M., Vergez L., Schmutz J., Larimer F., Land M.,
RA   Hauser L., Kyrpides N., Kim E., Tiedje J., Richardson P.;
RT   "Complete sequence of chromosome of Psychrobacter sp. PRwf-1.";
RL   Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the transfer of a methyl group from methyl-
CC       cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and
CC       methionine. Subsequently, remethylates the cofactor using
CC       methyltetrahydrofolate. {ECO:0000256|ARBA:ARBA00025552,
CC       ECO:0000256|PIRNR:PIRNR000381}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine =
CC         (6S)-5,6,7,8-tetrahydrofolate + L-methionine; Xref=Rhea:RHEA:11172,
CC         ChEBI:CHEBI:18608, ChEBI:CHEBI:57453, ChEBI:CHEBI:57844,
CC         ChEBI:CHEBI:58199; EC=2.1.1.13;
CC         Evidence={ECO:0000256|ARBA:ARBA00001700,
CC         ECO:0000256|PIRNR:PIRNR000381};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000256|ARBA:ARBA00001947,
CC         ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00333};
CC   -!- COFACTOR:
CC       Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC         Evidence={ECO:0000256|ARBA:ARBA00001956,
CC         ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC       pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
CC       {ECO:0000256|ARBA:ARBA00005178, ECO:0000256|PIRNR:PIRNR000381}.
CC   -!- DOMAIN: Modular enzyme with four functionally distinct domains. The
CC       isolated Hcy-binding domain catalyzes methyl transfer from free
CC       methylcobalamin to homocysteine. The Hcy-binding domain in association
CC       with the pterin-binding domain catalyzes the methylation of
CC       cob(I)alamin by methyltetrahydrofolate and the methylation of
CC       homocysteine. The B12-binding domain binds the cofactor. The AdoMet
CC       activation domain binds S-adenosyl-L-methionine. Under aerobic
CC       conditions cob(I)alamin can be converted to inactive cob(II)alamin.
CC       Reductive methylation by S-adenosyl-L-methionine and flavodoxin
CC       regenerates methylcobalamin. {ECO:0000256|PIRNR:PIRNR000381}.
CC   -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC       family. {ECO:0000256|ARBA:ARBA00010398}.
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DR   EMBL; CP000713; ABQ93550.1; -; Genomic_DNA.
DR   AlphaFoldDB; A5WD09; -.
DR   STRING; 349106.PsycPRwf_0595; -.
DR   KEGG; prw:PsycPRwf_0595; -.
DR   eggNOG; COG0646; Bacteria.
DR   eggNOG; COG1410; Bacteria.
DR   HOGENOM; CLU_004914_4_0_6; -.
DR   UniPathway; UPA00051; UER00081.
DR   GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0042558; P:pteridine-containing compound metabolic process; IEA:InterPro.
DR   CDD; cd02069; methionine_synthase_B12_BD; 1.
DR   CDD; cd00740; MeTr; 1.
DR   Gene3D; 3.40.50.280; Cobalamin-binding domain; 1.
DR   Gene3D; 1.10.288.10; Cobalamin-dependent Methionine Synthase, domain 2; 1.
DR   Gene3D; 3.20.20.20; Dihydropteroate synthase-like; 1.
DR   Gene3D; 3.20.20.330; Homocysteine-binding-like domain; 1.
DR   Gene3D; 1.10.1240.10; Methionine synthase domain; 1.
DR   Gene3D; 3.10.196.10; Vitamin B12-dependent methionine synthase, activation domain; 1.
DR   InterPro; IPR003759; Cbl-bd_cap.
DR   InterPro; IPR006158; Cobalamin-bd.
DR   InterPro; IPR036724; Cobalamin-bd_sf.
DR   InterPro; IPR011005; Dihydropteroate_synth-like_sf.
DR   InterPro; IPR003726; HCY_dom.
DR   InterPro; IPR036589; HCY_dom_sf.
DR   InterPro; IPR033706; Met_synthase_B12-bd.
DR   InterPro; IPR011822; MetH.
DR   InterPro; IPR036594; Meth_synthase_dom.
DR   InterPro; IPR000489; Pterin-binding_dom.
DR   InterPro; IPR004223; VitB12-dep_Met_synth_activ_dom.
DR   InterPro; IPR037010; VitB12-dep_Met_synth_activ_sf.
DR   NCBIfam; TIGR02082; metH; 1.
DR   PANTHER; PTHR45833; METHIONINE SYNTHASE; 1.
DR   PANTHER; PTHR45833:SF1; METHIONINE SYNTHASE; 1.
DR   Pfam; PF02310; B12-binding; 1.
DR   Pfam; PF02607; B12-binding_2; 1.
DR   Pfam; PF02965; Met_synt_B12; 1.
DR   Pfam; PF00809; Pterin_bind; 1.
DR   Pfam; PF02574; S-methyl_trans; 1.
DR   PIRSF; PIRSF000381; MetH; 1.
DR   SMART; SM01018; B12-binding_2; 1.
DR   SUPFAM; SSF52242; Cobalamin (vitamin B12)-binding domain; 1.
DR   SUPFAM; SSF51717; Dihydropteroate synthetase-like; 1.
DR   SUPFAM; SSF82282; Homocysteine S-methyltransferase; 1.
DR   SUPFAM; SSF56507; Methionine synthase activation domain-like; 1.
DR   SUPFAM; SSF47644; Methionine synthase domain; 1.
DR   PROSITE; PS50974; ADOMET_ACTIVATION; 1.
DR   PROSITE; PS51332; B12_BINDING; 1.
DR   PROSITE; PS51337; B12_BINDING_NTER; 1.
DR   PROSITE; PS50970; HCY; 1.
DR   PROSITE; PS50972; PTERIN_BINDING; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis {ECO:0000256|ARBA:ARBA00022605,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Cobalamin {ECO:0000256|ARBA:ARBA00022628, ECO:0000256|PIRNR:PIRNR000381};
KW   Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW   ECO:0000256|PIRNR:PIRNR000381}; Repeat {ECO:0000256|ARBA:ARBA00022737};
KW   S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381};
KW   Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRNR:PIRNR000381}.
FT   DOMAIN          47..367
FT                   /note="Hcy-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50970"
FT   DOMAIN          398..658
FT                   /note="Pterin-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50972"
FT   DOMAIN          695..789
FT                   /note="B12-binding N-terminal"
FT                   /evidence="ECO:0000259|PROSITE:PS51337"
FT   DOMAIN          791..927
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS51332"
FT   DOMAIN          943..1272
FT                   /note="AdoMet activation"
FT                   /evidence="ECO:0000259|PROSITE:PS50974"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        7..21
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         289
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT                   ECO:0000256|PROSITE-ProRule:PRU00333"
FT   BINDING         352
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT                   ECO:0000256|PROSITE-ProRule:PRU00333"
FT   BINDING         353
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT                   ECO:0000256|PROSITE-ProRule:PRU00333"
FT   BINDING         739
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         801..805
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         804
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /ligand_part="Co"
FT                   /ligand_part_id="ChEBI:CHEBI:27638"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-1"
FT   BINDING         849
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         853
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         906
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         993
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         1183
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         1238..1239
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ   SEQUENCE   1272 AA;  140989 MW;  EF63F634CBFEEDAB CRC64;
     MANCSHPEHN TKKDLPETAI KKGHNPDNFN LVPPAKFPFK EQQLTARQRI VEQLNQRILM
     LDGAMGTQIQ TFKLGESDYR GERFADFTQD VQGNNDLLVL TQPELIKSIH RDHLTAGADI
     IETNSFNGTQ ISMADYAMEH LVPEINKEAA RLAREVADEF TAQNPDKPRF VAGVIGPTSR
     TCSLSPDVND PAYRNVTFDE LVDNYTEALF ALIEGGIDLV LIETIFDTLN AKAAIFAVTG
     VFETIGFELP IMISGTITDA SGRTLSGQTA EAFYNSIRHA KPLSVGFNCA LGADALKPHI
     QTLSDIADTY ISAHPNAGLP NEFGEYDETP EQTAALLDGF GKSGLLNIVG GCCGTRPEHI
     KAIHDVMQKY PPRQIPTIAP ACRLSGLEPF TITKDSLFVN VGERTNVTGS KKFLRLIKTG
     EFTEALDVAR NQVDGGAQIV DINMDEGMLD SKGAMIHFLN LVAGEPDISR VPLMIDSSKW
     DIIEEGLKRT QGKSVVNSIS LKEGYDEFVK HAKLCMRYGA AVIVMAFDED GQADSYERKI
     QICQRSYDIL VNEVGFPSED IIFDPNIFAV ATGITEHNNY GADFINATRW ITDNLPNAMV
     SGGVSNVSFS FRGNPIREAI NAVFLYHAIQ AGLTMGIVNP AMLEVYDEIP KEARDAIEDV
     MLNRNQGESG QEATERLMTI AEAYVAGGKK NDGTIDLSWR EQSVEKRIEH ALVKGITTYI
     DEDTEEARLK YPKPLHVIEG PLMDGMNVVG DLFGAGKMFL PQVVKSARVM KRAVAVLNPY
     IEAEKVEGEV KGKVVMATVK GDVHDIGKNI VGVVLGCNGY DVVDLGVMVP CDKILDTAIA
     EKADIIGLSG LITPSLDEMV YVAKQMQERG MTLPLMIGGA TTSKAHTAVK IEPNYQNDAV
     IYVSDASRSV GVVTKLLSQE HRVELLRETR EEYQKVRERL ANRKPKAAKL SYQESIEQGF
     KFDWDNYTPP VPNEQGQIIF DNYPIENLLP YIDWTPFFVS WGLVGKYPKI FDDEVVGAEA
     KDLFANAKAL MQTFIDEQLV TPKGVFKIMP ARRTDHDTVT VYDKEPSAGG QPTHVFEHLR
     QQSDKASGKP NYSLADFISP SEDYDDYLGG FTVSIVGAQE LSDSYKEAGD DYNAIMVQAL
     CDRLAEAFAE HLHELIRTKY WGYQPTEQLT NEELIKEKYV GIRPAPGYPA CPEHTEKGKL
     FDWLDTTNAI GTYLTESFAM WPASSVSGFY YSHPESTYFN VGKIDRDQLE DYAKRKDWDI
     KTAEKWLNPN LT
//