O33259 (METH_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	metH
Ordered Locus Names:	Rv2124c
ORF Names:	MTCY261.20c

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	1192 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	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.
Catalytic activity	5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
Cofactor	Cobalamin By similarity. Binds 1 zinc ion per subunit By similarity.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
Domain	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.
Miscellaneous	L-homocysteine is bound via the zinc atom By similarity. Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the vitamin-B12 dependent methionine synthase family. Contains 1 AdoMet activation domain. Contains 1 B12-binding domain. Contains 1 B12-binding N-terminal domain. Contains 1 Hcy-binding domain. Contains 1 pterin-binding domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Domain	Repeat
Ligand	Cobalamin Cobalt Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pteridine-containing compound metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cell wall Inferred from direct assay PubMed 15525680. Source: MTBBASE cytosol Inferred from direct assay PubMed 15525680. Source: MTBBASE plasma membrane Inferred from direct assay PubMed 15525680. Source: MTBBASE
Molecular_function	cobalamin binding Inferred from electronic annotation. Source: UniProtKB-KW homocysteine S-methyltransferase activity Inferred from electronic annotation. Source: InterPro methionine synthase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1192	1192	Methionine synthase		PRO_0000204534
Regions
	Domain	1 – 312	312	Hcy-binding
	Domain	343 – 601	259	Pterin-binding
	Domain	635 – 728	94	B12-binding N-terminal
	Domain	729 – 866	138	B12-binding
	Domain	893 – 1192	300	AdoMet activation
	Region	819 – 820	2	Cobalamin-binding By similarity
	Region	1189 – 1190	2	S-adenosyl-L-methionine binding By similarity
Sites
	Metal binding	231	1	Zinc By similarity
	Metal binding	297	1	Zinc By similarity
	Metal binding	298	1	Zinc By similarity
	Metal binding	742	1	Cobalt (cobalamin axial ligand) By similarity
	Binding site	787	1	Cobalamin By similarity
	Binding site	940	1	S-adenosyl-L-methionine By similarity
	Binding site	1135	1	S-adenosyl-L-methionine; via carbonyl oxygen By similarity
	Binding site	1139	1	Cobalamin; via carbonyl oxygen By similarity

Sequences

	Sequence		Length	Mass (Da)
	O33259 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 820450DCE77BE15B	FASTA	1,192	130,323
	10 20 30 40 50 60 MTAADKHLYD TDLLDVLSQR VMVGDGAMGT QLQAADLTLD DFRGLEGCNE ILNETRPDVL 70 80 90 100 110 120 ETIHRNYFEA GADAVETNTF GCNLSNLGDY DIADRIRDLS QKGTAIARRV ADELGSPDRK 130 140 150 160 170 180 RYVLGSMGPG TKLPTLGHTE YAVIRDAYTE AALGMLDGGA DAILVETCQD LLQLKAAVLG 190 200 210 220 230 240 SRRAMTRAGR HIPVFAHVTV ETTGTMLLGS EIGAALTAVE PLGVDMIGLN CATGPAEMSE 250 260 270 280 290 300 HLRHLSRHAR IPVSVMPNAG LPVLGAKGAE YPLLPDELAE ALAGFIAEFG LSLVGGCCGT 310 320 330 340 350 360 TPAHIREVAA AVANIKRPER QVSYEPSVSS LYTAIPFAQD ASVLVIGERT NANGSKGFRE 370 380 390 400 410 420 AMIAEDYQKC LDIAKDQTRD GAHLLDLCVD YVGRDGVADM KALASRLATS STLPIMLDST 430 440 450 460 470 480 ETAVLQAGLE HLGGRCAINS VNYEDGDGPE SRFAKTMALV AEHGAAVVAL TIDEEGQART 490 500 510 520 530 540 AQKKVEIAER LINDITGNWG VDESSILIDT LTFTIATGQE ESRRDGIETI EAIRELKKRH 550 560 570 580 590 600 PDVQTTLGLS NISFGLNPAA RQVLNSVFLH ECQEAGLDSA IVHASKILPM NRIPEEQRNV 610 620 630 640 650 660 ALDLVYDRRR EDYDPLQELM RLFEGVSAAS SKEDRLAELA GLPLFERLAQ RIVDGERNGL 670 680 690 700 710 720 DADLDEAMTQ KPPLQIINEH LLAGMKTVGE LFGSGQMQLP FVLQSAEVMK AAVAYLEPHM 730 740 750 760 770 780 ERSDDDSGKG RIVLATVKGD VHDIGKNLVD IILSNNGYEV VNIGIKQPIA TILEVAEDKS 790 800 810 820 830 840 ADVVGMSGLL VKSTVVMKEN LEEMNTRGVA EKFPVLLGGA ALTRSYVEND LAEIYQGEVH 850 860 870 880 890 900 YARDAFEGLK LMDTIMSAKR GEAPDENSPE AIKAREKEAE RKARHQRSKR IAAQRKAAEE 910 920 930 940 950 960 PVEVPERSDV AADIEVPAPP FWGSRIVKGL AVADYTGLLD ERALFLGQWG LRGQRGGEGP 970 980 990 1000 1010 1020 SYEDLVETEG RPRLRYWLDR LSTDGILAHA AVVYGYFPAV SEGNDIVVLT EPKPDAPVRY 1030 1040 1050 1060 1070 1080 RFHFPRQQRG RFLCIADFIR SRELAAERGE VDVLPFQLVT MGQPIADFAN ELFASNAYRD 1090 1100 1110 1120 1130 1140 YLEVHGIGVQ LTEALAEYWH RRIREELKFS GDRAMAAEDP EAKEDYFKLG YRGARFAFGY 1150 1160 1170 1180 1190 GACPDLEDRA KMMALLEPER IGVTLSEELQ LHPEQSTDAF VLHHPEAKYF NV

References

[1]

"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.

[2]

"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842578 Genomic DNA. Translation: CAB10719.1. AL123456 Genomic DNA. Translation: CCP44899.1.
PIR	G70513.
RefSeq	NP_216640.1. NC_000962.3. YP_006515540.1. NC_018143.1.
3D structure databases
ProteinModelPortal	O33259.
SMR	O33259. Positions 16-619, 637-1192.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv2124c.
Proteomic databases
PRIDE	O33259.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	13316931. 888711.
KEGG	mtu:Rv2124c. mtv:RVBD_2124c.
PATRIC	18153284. VBIMycTub87468_2371.
Organism-specific databases
TubercuList	Rv2124c.
Phylogenomic databases
eggNOG	COG1410.
HOGENOM	HOG000251408.
KO	K00548.
OMA	NGSKAFR.
ProtClustDB	CLSK872016.
Enzyme and pathway databases
UniPathway	UPA00051; UER00081.
Family and domain databases
Gene3D	1.10.1240.10. 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.
InterPro	IPR003759. Cbl-bd_cap. IPR006158. Cobalamin-bd. IPR011005. Dihydropteroate_synth-like. IPR011822. MetH. IPR000489. Pterin-binding. IPR003726. S_MeTrfase. IPR004223. VitB12-dep_Met_synth_activ_dom. [Graphical view]
Pfam	PF02310. 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]
PIRSF	PIRSF000381. MetH. 1 hit.
SMART	SM01018. B12-binding_2. 1 hit. [Graphical view]
SUPFAM	SSF52242. Cbl-bd. 1 hit. SSF51717. DHP_synth_like. 1 hit. SSF56507. Met_synth_B12. 1 hit. SSF47644. Met_synth_Cbl-bd. 1 hit. SSF82282. S_methyl_trans. 1 hit.
TIGRFAMs	TIGR02082. metH. 1 hit.
PROSITE	PS50974. 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]
ProtoNet	Search...

Entry information

Entry name

METH_MYCTU

Accession

Primary (citable) accession number: O33259
Secondary accession number(s): L0T8Q3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program