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Protein

Methionine synthase

Gene

metH

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).By similarity

Catalytic activityi

5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.

Cofactori

Protein has several cofactor binding sites:

Pathwayi: L-methionine biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes L-methionine from L-homocysteine (MetH route).
Proteins known to be involved in this subpathway in this organism are:
  1. Methionine synthase (metH)
This subpathway is part of the pathway L-methionine biosynthesis via de novo pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-methionine from L-homocysteine (MetH route), the pathway L-methionine biosynthesis via de novo pathway and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi231ZincPROSITE-ProRule annotation1
Metal bindingi297ZincPROSITE-ProRule annotation1
Metal bindingi298ZincPROSITE-ProRule annotation1
Metal bindingi742Cobalt (cobalamin axial ligand)By similarity1
Binding sitei787CobalaminBy similarity1
Binding sitei940S-adenosyl-L-methionineBy similarity1
Binding sitei1135S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei1139Cobalamin; via carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Amino-acid biosynthesis, Methionine biosynthesis

Keywords - Ligandi

Cobalamin, Cobalt, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-6330-MONOMER.
UniPathwayiUPA00051; UER00081.

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine synthase (EC:2.1.1.13)
Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Methionine synthase, vitamin-B12 dependent
Short name:
MS
Gene namesi
Name:metH
Ordered Locus Names:Rv2124c
ORF Names:MTCY261.20c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv2124c.

Subcellular locationi

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • cytosol Source: MTBBASE
  • plasma membrane Source: MTBBASE
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002045341 – 1192Methionine synthaseAdd BLAST1192

Proteomic databases

PaxDbiO33259.

Interactioni

Protein-protein interaction databases

STRINGi83332.Rv2124c.

Structurei

3D structure databases

ProteinModelPortaliO33259.
SMRiO33259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 312Hcy-bindingPROSITE-ProRule annotationAdd BLAST312
Domaini343 – 601Pterin-bindingPROSITE-ProRule annotationAdd BLAST259
Domaini635 – 728B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST94
Domaini729 – 866B12-bindingPROSITE-ProRule annotationAdd BLAST138
Domaini893 – 1192AdoMet activationPROSITE-ProRule annotationAdd BLAST300

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni819 – 820Cobalamin-bindingBy similarity2
Regioni1189 – 1190S-adenosyl-L-methionine bindingBy similarity2

Domaini

Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).By similarity

Sequence similaritiesi

Contains 1 AdoMet activation domain.PROSITE-ProRule annotation
Contains 1 B12-binding domain.PROSITE-ProRule annotation
Contains 1 B12-binding N-terminal domain.PROSITE-ProRule annotation
Contains 1 Hcy-binding domain.PROSITE-ProRule annotation
Contains 1 pterin-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4105C3R. Bacteria.
COG0646. LUCA.
COG1410. LUCA.
HOGENOMiHOG000251408.
InParanoidiO33259.
KOiK00548.
OMAiDYNSIMV.
PhylomeDBiO33259.

Family and domain databases

CDDicd02069. methionine_synthase_B12_BD. 1 hit.
Gene3Di1.10.1240.10. 1 hit.
3.10.196.10. 1 hit.
3.20.20.20. 1 hit.
3.20.20.330. 1 hit.
3.40.50.280. 1 hit.
InterProiIPR003759. Cbl-bd_cap.
IPR006158. Cobalamin-bd.
IPR011005. Dihydropteroate_synth-like.
IPR003726. HCY_dom.
IPR033706. Met_synthase_B12-bd.
IPR011822. MetH.
IPR000489. Pterin-binding_dom.
IPR004223. VitB12-dep_Met_synth_activ_dom.
[Graphical view]
PfamiPF02310. B12-binding. 1 hit.
PF02607. B12-binding_2. 1 hit.
PF02965. Met_synt_B12. 1 hit.
PF00809. Pterin_bind. 1 hit.
PF02574. S-methyl_trans. 1 hit.
[Graphical view]
PIRSFiPIRSF000381. MetH. 1 hit.
SMARTiSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMiSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsiTIGR02082. metH. 1 hit.
PROSITEiPS50974. ADOMET_ACTIVATION. 1 hit.
PS51332. B12_BINDING. 1 hit.
PS51337. B12_BINDING_NTER. 1 hit.
PS50970. HCY. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O33259-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAADKHLYD TDLLDVLSQR VMVGDGAMGT QLQAADLTLD DFRGLEGCNE
60 70 80 90 100
ILNETRPDVL ETIHRNYFEA GADAVETNTF GCNLSNLGDY DIADRIRDLS
110 120 130 140 150
QKGTAIARRV ADELGSPDRK RYVLGSMGPG TKLPTLGHTE YAVIRDAYTE
160 170 180 190 200
AALGMLDGGA DAILVETCQD LLQLKAAVLG SRRAMTRAGR HIPVFAHVTV
210 220 230 240 250
ETTGTMLLGS EIGAALTAVE PLGVDMIGLN CATGPAEMSE HLRHLSRHAR
260 270 280 290 300
IPVSVMPNAG LPVLGAKGAE YPLLPDELAE ALAGFIAEFG LSLVGGCCGT
310 320 330 340 350
TPAHIREVAA AVANIKRPER QVSYEPSVSS LYTAIPFAQD ASVLVIGERT
360 370 380 390 400
NANGSKGFRE AMIAEDYQKC LDIAKDQTRD GAHLLDLCVD YVGRDGVADM
410 420 430 440 450
KALASRLATS STLPIMLDST ETAVLQAGLE HLGGRCAINS VNYEDGDGPE
460 470 480 490 500
SRFAKTMALV AEHGAAVVAL TIDEEGQART AQKKVEIAER LINDITGNWG
510 520 530 540 550
VDESSILIDT LTFTIATGQE ESRRDGIETI EAIRELKKRH PDVQTTLGLS
560 570 580 590 600
NISFGLNPAA RQVLNSVFLH ECQEAGLDSA IVHASKILPM NRIPEEQRNV
610 620 630 640 650
ALDLVYDRRR EDYDPLQELM RLFEGVSAAS SKEDRLAELA GLPLFERLAQ
660 670 680 690 700
RIVDGERNGL DADLDEAMTQ KPPLQIINEH LLAGMKTVGE LFGSGQMQLP
710 720 730 740 750
FVLQSAEVMK AAVAYLEPHM ERSDDDSGKG RIVLATVKGD VHDIGKNLVD
760 770 780 790 800
IILSNNGYEV VNIGIKQPIA TILEVAEDKS ADVVGMSGLL VKSTVVMKEN
810 820 830 840 850
LEEMNTRGVA EKFPVLLGGA ALTRSYVEND LAEIYQGEVH YARDAFEGLK
860 870 880 890 900
LMDTIMSAKR GEAPDENSPE AIKAREKEAE RKARHQRSKR IAAQRKAAEE
910 920 930 940 950
PVEVPERSDV AADIEVPAPP FWGSRIVKGL AVADYTGLLD ERALFLGQWG
960 970 980 990 1000
LRGQRGGEGP SYEDLVETEG RPRLRYWLDR LSTDGILAHA AVVYGYFPAV
1010 1020 1030 1040 1050
SEGNDIVVLT EPKPDAPVRY RFHFPRQQRG RFLCIADFIR SRELAAERGE
1060 1070 1080 1090 1100
VDVLPFQLVT MGQPIADFAN ELFASNAYRD YLEVHGIGVQ LTEALAEYWH
1110 1120 1130 1140 1150
RRIREELKFS GDRAMAAEDP EAKEDYFKLG YRGARFAFGY GACPDLEDRA
1160 1170 1180 1190
KMMALLEPER IGVTLSEELQ LHPEQSTDAF VLHHPEAKYF NV
Length:1,192
Mass (Da):130,323
Last modified:January 1, 1998 - v1
Checksum:i820450DCE77BE15B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP44899.1.
PIRiG70513.
RefSeqiNP_216640.1. NC_000962.3.
WP_003900472.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP44899; CCP44899; Rv2124c.
GeneIDi888711.
KEGGimtu:Rv2124c.
PATRICi18153284. VBIMycTub87468_2371.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP44899.1.
PIRiG70513.
RefSeqiNP_216640.1. NC_000962.3.
WP_003900472.1. NZ_KK339370.1.

3D structure databases

ProteinModelPortaliO33259.
SMRiO33259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv2124c.

Proteomic databases

PaxDbiO33259.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP44899; CCP44899; Rv2124c.
GeneIDi888711.
KEGGimtu:Rv2124c.
PATRICi18153284. VBIMycTub87468_2371.

Organism-specific databases

TubercuListiRv2124c.

Phylogenomic databases

eggNOGiENOG4105C3R. Bacteria.
COG0646. LUCA.
COG1410. LUCA.
HOGENOMiHOG000251408.
InParanoidiO33259.
KOiK00548.
OMAiDYNSIMV.
PhylomeDBiO33259.

Enzyme and pathway databases

UniPathwayiUPA00051; UER00081.
BioCyciMTBH37RV:G185E-6330-MONOMER.

Family and domain databases

CDDicd02069. methionine_synthase_B12_BD. 1 hit.
Gene3Di1.10.1240.10. 1 hit.
3.10.196.10. 1 hit.
3.20.20.20. 1 hit.
3.20.20.330. 1 hit.
3.40.50.280. 1 hit.
InterProiIPR003759. Cbl-bd_cap.
IPR006158. Cobalamin-bd.
IPR011005. Dihydropteroate_synth-like.
IPR003726. HCY_dom.
IPR033706. Met_synthase_B12-bd.
IPR011822. MetH.
IPR000489. Pterin-binding_dom.
IPR004223. VitB12-dep_Met_synth_activ_dom.
[Graphical view]
PfamiPF02310. B12-binding. 1 hit.
PF02607. B12-binding_2. 1 hit.
PF02965. Met_synt_B12. 1 hit.
PF00809. Pterin_bind. 1 hit.
PF02574. S-methyl_trans. 1 hit.
[Graphical view]
PIRSFiPIRSF000381. MetH. 1 hit.
SMARTiSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMiSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsiTIGR02082. metH. 1 hit.
PROSITEiPS50974. ADOMET_ACTIVATION. 1 hit.
PS51332. B12_BINDING. 1 hit.
PS51337. B12_BINDING_NTER. 1 hit.
PS50970. HCY. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMETH_MYCTU
AccessioniPrimary (citable) accession number: O33259
Secondary accession number(s): L0T8Q3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

L-homocysteine is bound via the zinc atom.By similarity
Was identified as a high-confidence drug target.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.