P0A817 (METK_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
S-adenosylmethionine synthase
Short name=AdoMet synthase
EC=2.5.1.6

Alternative name(s):
MAT
Methionine adenosyltransferase

Gene names

Name:	metK
Synonyms:	metX
Ordered Locus Names:	b2942, JW2909

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	384 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme. Is essential for growth. HAMAP-Rule MF_00086
Catalytic activity	ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L-methionine. HAMAP-Rule MF_00086
Cofactor	Binds 2 divalent ions per subunit. Magnesium or cobalt. Binds 1 potassium ion per subunit.
Pathway	Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1. HAMAP-Rule MF_00086
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm HAMAP-Rule MF_00086.
Induction	AdoMet activates the tripolyphosphatase reaction. HAMAP-Rule MF_00086
Disruption phenotype	Cells are resistant to methionine-analogs, such as DL-ethionine(Et). Ref.2
Sequence similarities	Belongs to the AdoMet synthase family.
Caution	Was originally (Ref.2) thought to differ from MetX, which was assigned as a second AdoMet synthase before being shown to be identical to MetK.
Mass spectrometry	Molecular mass is 41843±10.5 Da from positions 2 - 384. Determined by ESI. Ref.14

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm
Ligand	ATP-binding Cobalt Magnesium Metal-binding Nucleotide-binding Potassium
Molecular function	Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	S-adenosylmethionine biosynthetic process Inferred from mutant phenotype PubMed 2115868PubMed 4577753. Source: EcoCyc one-carbon metabolic process Inferred from electronic annotation. Source: HAMAP
Cellular_component	cytosol Inferred from direct assay PubMed 16858726. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: HAMAP magnesium ion binding Inferred from direct assay PubMed 6251075. Source: EcoCyc methionine adenosyltransferase activity Inferred from direct assay PubMed 6251075. Source: EcoCyc potassium ion binding Inferred from direct assay PubMed 6251075. Source: EcoCyc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-546295,EBI-546295

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed HAMAP-Rule MF_00086

Chain

2 – 384

383

S-adenosylmethionine synthase HAMAP-Rule MF_00086

PRO_0000174518

Regions

Nucleotide binding

260 – 267

8

ATP Potential

Region

239 – 248

10

Pyrophosphate binding HAMAP-Rule MF_00086

Sites

Metal binding

17

1

Magnesium

Metal binding

43

1

Potassium

Metal binding

264

1

Potassium

Metal binding

272

1

Magnesium

Binding site

119

1

Methionine

Binding site

239

1

Methionine

Amino acid modifications

Modified residue

3

1

N6-acetyllysine Ref.13

Experimental info

Mutagenesis

15

1

H → N: Loss of activity. Ref.11

Mutagenesis

17

1

D → N or A: Loss of activity. Ref.10

Mutagenesis

43

1

E → K: Misfolding and subject to proteolytic degradation. Ref.6

Mutagenesis

43

1

E → Q: Loss of stimulation by potassium. Ref.6

Mutagenesis

90

1

C → A or S: Decrease in the homotetramer formation capability. Enhanced thermal stability. Ref.7

Mutagenesis

119

1

D → N: Decrease of both AdoMet synthesis and AdoMet-activated tripolyphosphate hydrolysis. Ref.10

Mutagenesis

166

1

K → M: Decrease in AdoMet synthesis. Ref.11

Mutagenesis

239

1

D → N: Decrease in AdoMet synthesis. Ref.10

Mutagenesis

240

1

C → A: Decrease in AdoMet synthesis. Ref.7

Mutagenesis

245

1

R → H or L: Loss of activity. Ref.9

Mutagenesis

246

1

K → M: Loss of activity. modification in protein conformation. Ref.11

Mutagenesis

266

1

K → A: Loss of activity. Ref.11

Mutagenesis

266

1

K → M: Unstable; trace activity. Ref.11

Mutagenesis

270

1

K → M: Decrease in activity. Ref.11

Mutagenesis

272

1

D → N or A: Loss of activity. Ref.10

Sequence conflict

50 – 61

12

MVLVG…ITTSA → IGFSWRRNHHQRP Ref.1

Sequence conflict

50 – 61

12

MVLVG…ITTSA → IGFSWRRNHHQRP Ref.5

Sequence conflict

123 – 133

11

MFGYATNETDV → DVSATQLMKPTC in AAA24164. Ref.1

Sequence conflict

159 – 161

3

PWL → RV Ref.1

Sequence conflict

159 – 161

3

PWL → RV Ref.2

Sequence conflict

172

1

Q → S in AAA24164. Ref.1

Sequence conflict

252

1

Y → T in AAA24164. Ref.1

Sequence conflict

305

1

V → L in AAA24164. Ref.1

Sequence conflict

337

1

Missing Ref.1

Sequence conflict

339

1

Y → I Ref.1

Sequence conflict

375 – 376

2

QL → HV Ref.2

Sequence conflict

378

1

R → P Ref.2

Secondary structure

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384

Helix Strand Turn

Details...

Beta strand

4 – 11

8

Helix

16 – 34

19

Beta strand

39 – 47

9

Beta strand

50 – 58

9

Helix

65 – 76

12

Helix

81 – 83

3

Turn

87 – 89

3

Beta strand

90 – 97

8

Helix

101 – 107

7

Turn

112 – 114

3

Beta strand

117 – 119

3

Beta strand

121 – 128

8

Helix

137 – 154

18

Beta strand

156 – 158

3

Beta strand

161 – 174

14

Beta strand

177 – 190

14

Beta strand

192 – 194

3

Helix

196 – 206

11

Turn

207 – 211

5

Helix

214 – 216

3

Beta strand

222 – 226

5

Helix

235 – 238

4

Beta strand

239 – 242

4

Turn

247 – 254

8

Helix

271 – 288

18

Beta strand

291 – 301

11

Beta strand

309 – 314

6

Beta strand

319 – 321

3

Helix

323 – 333

11

Helix

338 – 345

8

Beta strand

348 – 350

3

Helix

353 – 356

4

Beta strand

360 – 362

3

Beta strand

364 – 366

3

Turn

367 – 369

3

Helix

373 – 379

7

Turn

380 – 382

3

Sequences

	Sequence		Length	Mass (Da)
	P0A817 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 97FA8CF17B542941	FASTA	384	41,952
	10 20 30 40 50 60 MAKHLFTSES VSEGHPDKIA DQISDAVLDA ILEQDPKARV ACETYVKTGM VLVGGEITTS 70 80 90 100 110 120 AWVDIEEITR NTVREIGYVH SDMGFDANSC AVLSAIGKQS PDINQGVDRA DPLEQGAGDQ 130 140 150 160 170 180 GLMFGYATNE TDVLMPAPIT YAHRLVQRQA EVRKNGTLPW LRPDAKSQVT FQYDDGKIVG 190 200 210 220 230 240 IDAVVLSTQH SEEIDQKSLQ EAVMEEIIKP ILPAEWLTSA TKFFINPTGR FVIGGPMGDC 250 260 270 280 290 300 GLTGRKIIVD TYGGMARHGG GAFSGKDPSK VDRSAAYAAR YVAKNIVAAG LADRCEIQVS 310 320 330 340 350 360 YAIGVAEPTS IMVETFGTEK VPSEQLTLLV REFFDLRPYG LIQMLDLLHP IYKETAAYGH 370 380 FGREHFPWEK TDKAQLLRDA AGLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The sequence of metK, the structural gene for S-adenosylmethionine synthetase in Escherichia coli." Markham G.D., Deparasis J., Gatmaitan J. J. Biol. Chem. 259:14505-14507(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Isozymes of S-adenosylmethionine synthetase are encoded by tandemly duplicated genes in Escherichia coli." Satishchandran C., Taylor J.C., Markham G.D. Mol. Microbiol. 9:835-846(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE. Strain: K12.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Nucleotide sequence and analysis of the speA gene encoding biosynthetic arginine decarboxylase in Escherichia coli." Moore R.C., Boyle S.M. J. Bacteriol. 172:4631-4640(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63.
[6]	"Investigation of monovalent cation activation of S-adenosylmethionine synthetase using mutagenesis and uranyl inhibition." McQueney M.S., Markham G.D. J. Biol. Chem. 270:18277-18284(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-43.
[7]	"Structural and functional roles of cysteine 90 and cysteine 240 in S-adenosylmethionine synthetase." Reczkowski R.S., Markham G.D. J. Biol. Chem. 270:18484-18490(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-90 AND CYS-240. Strain: B and K12.
[8]	"Escherichia coli proteome analysis using the gene-protein database." VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C. Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY 2D-GEL.
[9]	"The active-site arginine of S-adenosylmethionine synthetase orients the reaction intermediate." Reczkowski R.S., Taylor J.C., Markham G.D. Biochemistry 37:13499-13506(1998) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-245. Strain: B and K12.
[10]	"The bifunctional active site of S-adenosylmethionine synthetase. Roles of the active site aspartates." Taylor J.C., Markham G.D. J. Biol. Chem. 274:32909-32914(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-17; ASP-119; ASP-239 AND ASP-272. Strain: B and K12.
[11]	"The bifunctional active site of S-adenosylmethionine synthetase. Roles of the basic residues." Taylor J.C., Markham G.D. J. Biol. Chem. 275:4060-4065(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-15; LYS-166; LYS-246; LYS-266 AND LYS-270. Strain: B and K12.
[12]	"Studies on the role of the metK gene product of Escherichia coli K-12." Wei Y., Newman E.B. Mol. Microbiol. 43:1651-1656(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL START SITE, ESSENTIAL GENE.
[13]	"Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F., Grishin N.V., Zhao Y. Mol. Cell. Proteomics 8:215-225(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3, MASS SPECTROMETRY. Strain: K12 / JW1106 and K12 / MG1655 / ATCC 47076.
[14]	"Crystal structure of S-adenosylmethionine synthetase." Takusagawa F., Kamitori S., Misaki S., Markham G.D. J. Biol. Chem. 271:136-147(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), MASS SPECTROMETRY.
[15]	"Structure and function of S-adenosylmethionine synthetase: crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 2.8-A resolution." Takusagawa F., Kamitori S., Markham G.D. Biochemistry 35:2586-2596(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[16]	"Flexible loop in the structure of S-adenosylmethionine synthetase crystallized in the tetragonal modification." Fu Z., Hu Y., Markham G.D., Takusagawa F. J. Biomol. Struct. Dyn. 13:727-739(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K02129 Genomic DNA. Translation: AAA24164.1.
U28377 Genomic DNA. Translation: AAA69109.1.
U00096 Genomic DNA. Translation: AAC75979.1.
AP009048 Genomic DNA. Translation: BAE77005.1.
M98266 Genomic DNA. Translation: AAB05197.1.
M31770 Genomic DNA. Translation: AAA24645.2.

PIR

SYECSM. E65079.

RefSeq

NP_417417.1. NC_000913.2.
YP_491141.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FUG	X-ray	3.20	A/B	2-384	[»]
1MXA	X-ray	2.80	A	2-384	[»]
1MXB	X-ray	2.80	A	2-384	[»]
1MXC	X-ray	3.00	A	2-384	[»]
1P7L	X-ray	2.50	A/B/C/D	2-383	[»]
1RG9	X-ray	2.50	A/B/C/D	2-383	[»]
1XRA	X-ray	3.00	A	2-384	[»]
1XRB	X-ray	3.00	A	2-384	[»]
1XRC	X-ray	3.00	A	2-384	[»]

ProteinModelPortal

P0A817.

SMR

P0A817. Positions 2-384.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35672N.

IntAct

P0A817. 37 interactions.

MINT

MINT-1233798.

STRING

511145.b2942.

PTM databases

PhosSite

P0809415.

2D gel databases

SWISS-2DPAGE

P0A817.

Proteomic databases

PaxDb

P0A817.

PRIDE

P0A817.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC75979; AAC75979; b2942.
BAE77005; BAE77005; BAE77005.

GeneID

12931663.
945389.

KEGG

ecj:Y75_p2872.
eco:b2942.

PATRIC

32121294. VBIEscCol129921_3035.

Organism-specific databases

EchoBASE

EB0584.

EcoGene

EG10589. metK.

Phylogenomic databases

eggNOG

COG0192.

HOGENOM

HOG000245710.

KO

K00789.

OMA

IYYAHRL.

ProtClustDB

PRK05250.

Enzyme and pathway databases

BioCyc

EcoCyc:S-ADENMETSYN-MONOMER.
ECOL316407:JW2909-MONOMER.
MetaCyc:S-ADENMETSYN-MONOMER.

SABIO-RK

P0A817.

UniPathway

UPA00315; UER00080.

Gene expression databases

Genevestigator

P0A817.

Family and domain databases

HAMAP

MF_00086. S-AdoMet_synth1.

InterPro

IPR022631. ADOMET_SYNTHASE_CS.
IPR022630. S-AdoMet_synt_C.
IPR022629. S-AdoMet_synt_central.
IPR022628. S-AdoMet_synt_N.
IPR002133. S-AdoMet_synthetase.
IPR022636. S-AdoMet_synthetase_sfam.
[Graphical view]

PANTHER

PTHR11964. PTHR11964. 1 hit.

Pfam

PF02773. S-AdoMet_synt_C. 1 hit.
PF02772. S-AdoMet_synt_M. 1 hit.
PF00438. S-AdoMet_synt_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000497. MAT. 1 hit.

SUPFAM

SSF55973. S-AdoMet_synt. 3 hits.

TIGRFAMs

TIGR01034. metK. 1 hit.

PROSITE

PS00376. ADOMET_SYNTHASE_1. 1 hit.
PS00377. ADOMET_SYNTHASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0A817.

Entry information

Entry name

METK_ECOLI

Accession

Primary (citable) accession number: P0A817
Secondary accession number(s): P04384, P30869, Q2M9Q1

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program