Reviewed, UniProtKB/Swiss-Prot P22188 (MURE_ECOLI)

Names and origin

Protein names

Recommended name:
    UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase
    EC=6.3.2.13
Alternative name(s):
    UDP-MurNAc-L-Ala-D-Glu:meso-diaminopimelate ligase
    Meso-diaminopimelate-adding enzyme
    Meso-A2pm-adding enzyme
    UDP-N-acetylmuramyl-tripeptide synthetase
    UDP-MurNAc-tripeptide synthetase

Gene names

Name:	murE
Ordered Locus Names:	b0085, JW0083

Organism

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

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	495 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 addition of meso-diaminopimelic acid to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan. Is also able to use many meso-diaminopimelate analogs as substrates, although much less efficiently, but not L-lysine. Ref.7 Ref.8 Ref.10
Catalytic activity	ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diamino-heptanedioate. HAMAP MF_00208
Enzyme regulation	Activated by potassium phosphate. Ref.7
Pathway	Cell wall biogenesis; peptidoglycan biosynthesis. HAMAP MF_00208
Subcellular location	Cytoplasm Probable HAMAP MF_00208.
Post-translational modification	Carbamoylation is probably crucial for Mg2+ binding and, consequently, for the gamma-phosphate positioning of ATP. HAMAP MF_00208
Sequence similarities	Belongs to the murCDEF family. MurE subfamily.
Biophysicochemical properties	Kinetic parameters: KM=76 µM for UDP-N-acetylmuramoyl-L-Ala-D-Glu Ref.9 KM=36 µM for meso-diaminopimelate KM=1500 µM for meso-lanthionine KM=3900 µM for L-allo-cystathionine KM=10000 µM for D-allo-cystathionine KM=620 µM for ATP Vmax=32 nmol/min/mg enzyme with meso-diaminopimelate as substrate Vmax=23 nmol/min/mg enzyme with meso-lanthionine as substrate Vmax=19 nmol/min/mg enzyme with L-allo-cystathionine as substrate Vmax=23 nmol/min/mg enzyme with L-allo-cystathionine as substrate pH dependence: Optimum pH is about 8.

Ontologies

Keywords
Biological process	Cell cycle Cell division Cell shape Cell wall biogenesis/degradation Peptidoglycan synthesis
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular cell wall organization Inferred from electronic annotation. Source: UniProtKB-KW peptidoglycan biosynthetic process Inferred from electronic annotation. Source: HAMAP regulation of cell shape Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: HAMAP UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase activity Ref.7 Inferred from direct assay. Source: UniProtKB UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
carA	P0A6F1	1	EBI-553061,EBI-546107

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7 Ref.6

Chain

2 – 495

494

UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase HAMAP MF_00208

PRO_0000101893

Regions

Nucleotide binding

116 – 122

7

ATP Potential

Region

44 – 46

3

UDP-MurNAc-L-Ala-D-Glu binding HAMAP MF_00208

Region

158 – 159

2

UDP-MurNAc-L-Ala-D-Glu binding HAMAP MF_00208

Region

414 – 417

4

Meso-diaminopimelate binding HAMAP MF_00208

Motif

414 – 417

4

Meso-diaminopimelate recognition motif HAMAP MF_00208

Sites

Binding site

27

1

UDP-MurNAc-L-Ala-D-Glu; via carbonyl oxygen HAMAP MF_00208

Binding site

29

1

UDP-MurNAc-L-Ala-D-Glu HAMAP MF_00208

Binding site

157

1

UDP-MurNAc-L-Ala-D-Glu HAMAP MF_00208

Binding site

185

1

UDP-MurNAc-L-Ala-D-Glu HAMAP MF_00208

Binding site

191

1

UDP-MurNAc-L-Ala-D-Glu HAMAP MF_00208

Binding site

193

1

UDP-MurNAc-L-Ala-D-Glu HAMAP MF_00208

Binding site

390

1

Meso-diaminopimelate HAMAP MF_00208

Binding site

465

1

Meso-diaminopimelate; via carbonyl oxygen HAMAP MF_00208

Binding site

469

1

Meso-diaminopimelate HAMAP MF_00208

Amino acid modifications

Modified residue

225

1

N6-carboxylysine HAMAP MF_00208

Natural variations

Natural variant

344

1

E → K in murE1.

Natural variant

495

1

A → S in murE1.

Secondary structure

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495

Helix Strand Turn

Details...

Helix

6 – 10

5

Turn

11 – 13

3

Beta strand

25 – 27

3

Helix

29 – 31

3

Beta strand

37 – 40

4

Helix

48 – 51

4

Helix

52 – 57

6

Beta strand

61 – 66

6

Turn

68 – 70

3

Beta strand

76 – 79

4

Beta strand

82 – 87

6

Helix

90 – 101

12

Helix

105 – 107

3

Beta strand

108 – 118

11

Helix

120 – 133

14

Beta strand

138 – 142

5

Beta strand

145 – 148

4

Beta strand

156 – 159

4

Helix

162 – 174

13

Beta strand

179 – 183

5

Helix

186 – 190

5

Turn

191 – 196

6

Beta strand

200 – 204

5

Helix

212 – 215

4

Helix

218 – 230

13

Beta strand

236 – 240

5

Helix

244 – 250

7

Beta strand

257 – 263

7

Turn

267 – 269

3

Beta strand

271 – 281

11

Beta strand

286 – 292

7

Beta strand

297 – 301

5

Helix

306 – 321

16

Helix

326 – 332

7

Helix

333 – 335

3

Beta strand

342 – 346

5

Beta strand

353 – 357

5

Helix

362 – 374

13

Beta strand

380 – 384

5

Beta strand

388 – 390

3

Helix

394 – 405

12

Beta strand

407 – 411

5

Helix

421 – 429

9

Helix

435 – 437

3

Beta strand

438 – 440

3

Helix

444 – 454

11

Beta strand

460 – 465

6

Beta strand

471 – 474

4

Beta strand

477 – 480

4

Helix

483 – 491

9

Sequences

	Sequence		Length	Mass (Da)
	P22188-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: D4A7A3E56D6C7E49	FASTA	495	53,344
	10 20 30 40 50 60 MADRNLRDLL APWVPDAPSR ALREMTLDSR VAAAGDLFVA VVGHQADGRR YIPQAIAQGV 70 80 90 100 110 120 AAIIAEAKDE ATDGEIREMH GVPVIYLSQL NERLSALAGR FYHEPSDNLR LVGVTGTNGK 130 140 150 160 170 180 TTTTQLLAQW SQLLGEISAV MGTVGNGLLG KVIPTENTTG SAVDVQHELA GLVDQGATFC 190 200 210 220 230 240 AMEVSSHGLV QHRVAALKFA ASVFTNLSRD HLDYHGDMEH YEAAKWLLYS EHHCGQAIIN 250 260 270 280 290 300 ADDEVGRRWL AKLPDAVAVS MEDHINPNCH GRWLKATEVN YHDSGATIRF SSSWGDGEIE 310 320 330 340 350 360 SHLMGAFNVS NLLLALATLL ALGYPLADLL KTAARLQPVC GRMEVFTAPG KPTVVVDYAH 370 380 390 400 410 420 TPDALEKALQ AARLHCAGKL WCVFGCGGDR DKGKRPLMGA IAEEFADVAV VTDDNPRTEE 430 440 450 460 470 480 PRAIINDILA GMLDAGHAKV MEGRAEAVTC AVMQAKENDV VLVAGKGHED YQIVGNQRLD 490 YSDRVTVARL LGVIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the murE gene of Escherichia coli." Tao J.-S., Ishiguro E.E. Can. J. Microbiol. 35:1051-1054(1989) [PubMed: 2692800] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region." Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A. Nucleic Acids Res. 20:3305-3308(1992) [PubMed: 1630901] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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: 9278503] [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: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Conditionally lethal Escherichia coli murein mutants contain point defects that map to regions conserved among murein and folyl poly-gamma-glutamate ligases: identification of a ligase superfamily." Eveland S.S., Pompliano D.L., Anderson M.S. Biochemistry 36:6223-6229(1997) [PubMed: 9166795] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], MUTANT MURE1. Strain: CGSC 5989.
[6]	"Revised interpretation of the sequence containing the murE gene encoding the UDP-N-acetylmuramyl-tripeptide synthetase of Escherichia coli." Michaud C., Parquet C., Flouret B., Blanot D., van Heijenoort J. Biochem. J. 269:277-278(1990) [PubMed: 2198024] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-124, PROTEIN SEQUENCE OF 2-19, SEQUENCE REVISION.
[7]	"Over-production, purification and properties of the uridine-diphosphate-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-2,6-diaminopimelate ligase from Escherichia coli." Michaud C., Mengin-Lecreulx D., van Heijenoort J., Blanot D. Eur. J. Biochem. 194:853-861(1990) [PubMed: 2269304] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-19, FUNCTION, CHARACTERIZATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBSTRATE SPECIFICITY.
[8]	"Specificity of the uridine-diphosphate-N-acetylmuramyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate synthetase from Escherichia coli." Abo-Ghalia M., Michaud C., Blanot D., van Heijenoort J. Eur. J. Biochem. 153:81-87(1985) [PubMed: 3905407] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY.
[9]	"Replacement of diaminopimelic acid by cystathionine or lanthionine in the peptidoglycan of Escherichia coli." Mengin-Lecreulx D., Blanot D., van Heijenoort J. J. Bacteriol. 176:4321-4327(1994) [PubMed: 8021219] [Abstract] Cited for: KINETIC PARAMETERS, SUBSTRATE SPECIFICITY.
[10]	"Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli." Gordon E., Flouret B., Chantalat L., van Heijenoort J., Mengin-Lecreulx D., Dideberg O. J. Biol. Chem. 276:10999-11006(2001) [PubMed: 11124264] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH PRODUCT, FUNCTION, CARBAMOYLATION AT LYS-225.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X55814 Genomic DNA. Translation: CAA39334.1.
X55034 Genomic DNA. Translation: CAA38862.1.
U00096 Genomic DNA. Translation: AAC73196.1.
AP009048 Genomic DNA. Translation: BAB96653.1.
U67894 Genomic DNA. Translation: AAB60789.1.

PIR

S14384.

RefSeq

AP_000748.1.
NP_414627.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E8C	X-ray	2.00	A/B	2-495	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-10280N.

IntAct

P22188. 15 interactions.

STRING

P22188.

2-D gel databases

SWISS-2DPAGE

P22188.

ECO2DBASE

F051.0. 6TH EDITION.

Genome annotation databases

GeneID

944791.

GenomeReviews

Gene locus JW0083 in contig AP009048_GR.
Gene locus b0085 in contig U00096_GR.

KEGG

ecj:JW0083.
eco:b0085.

Organism-specific databases

EchoBASE

EB0616.

EcoGene

EG10621. murE.

CMR

Search...

Phylogenomic databases

eggNOG

COG0769.

HOGENOM

HBG602753.

OMA

HTPDGIE.

Enzyme and pathway databases

BioCyc

EcoCyc:UDP-NACMURALGLDAPLIG-MONOMER.
ECOL168927:B0085-MONOMER.
MetaCyc:UDP-NACMURALGLDAPLIG-MONOMER.

Gene expression databases

Genevestigator

P22188.

Family and domain databases

HAMAP

MF_00208. MurE.
[Tree]

InterPro

IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
IPR000713. Mur_ligase_N.
IPR005761. UDP-N-AcMur-Glu-dNH2Pim_ligase.
[Graphical view]

Gene3D

G3DSA:3.90.190.20. Mur_ligase_C. 1 hit.
G3DSA:3.40.1190.10. Mur_ligase_cen. 1 hit.

Pfam

PF01225. Mur_ligase. 1 hit.
PF02875. Mur_ligase_C. 1 hit.
PF08245. Mur_ligase_M. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01085. murE. 1 hit.

ProtoNet

Search...

Entry information

Entry name

MURE_ECOLI

Accession

Primary (citable) accession number: P22188
Secondary accession number(s): O07101

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)