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P0ACC7 (GLMU_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional protein GlmU

Including the following 2 domains:

  1. UDP-N-acetylglucosamine pyrophosphorylase
    EC=2.7.7.23
    Alternative name(s):
    N-acetylglucosamine-1-phosphate uridyltransferase
  2. Glucosamine-1-phosphate N-acetyltransferase
    EC=2.3.1.157
Gene names
Name:glmU
Synonyms:yieA
Ordered Locus Names:b3730, JW3708
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length456 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain. Ref.6 Ref.7

Catalytic activity

Acetyl-CoA + alpha-D-glucosamine 1-phosphate = CoA + N-acetyl-alpha-D-glucosamine 1-phosphate. Ref.7

UTP + N-acetyl-alpha-D-glucosamine 1-phosphate = diphosphate + UDP-N-acetyl-alpha-D-glucosamine. Ref.7

Cofactor

Binds 1 magnesium ion per subunit. Can also use cobalt ions to a lesser extent. Ref.10

Enzyme regulation

Inhibited by its reaction product N-acetylglucosamine-1-phosphate and by UDP-N-acetylmuramic acid, which is one of the first precursors specific for the peptidoglycan pathway. Ref.6 Ref.12 Ref.13

Pathway

Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-glucosamine biosynthesis; N-acetyl-alpha-D-glucosamine 1-phosphate from alpha-D-glucosamine 6-phosphate (route II): step 2/2. HAMAP-Rule MF_01631

Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-glucosamine biosynthesis; UDP-N-acetyl-alpha-D-glucosamine from N-acetyl-alpha-D-glucosamine 1-phosphate: step 1/1.

Bacterial outer membrane biogenesis; LPS lipid A biosynthesis. HAMAP-Rule MF_01631

Subunit structure

Homotrimer. In vivo forms a hexameric aggregate. Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location

Cytoplasm HAMAP-Rule MF_01631.

Sequence similarities

In the N-terminal section; belongs to the N-acetylglucosamine-1-phosphate uridyltransferase family.

In the C-terminal section; belongs to the transferase hexapeptide repeat family.

Biophysicochemical properties

Kinetic parameters:

KM=0.018 mM for N-acetylglucosamine 1-phosphate Ref.6 Ref.7 Ref.8

KM=0.15 mM for alpha-D-glucosamine 1-phosphate

KM=0.25 mM for alpha-D-glucosamine 1-phosphate

KM=0.32 mM for acetyl-CoA

KM=0.6 mM for acetyl-CoA

KM=0.84 mM for n-propionyl-CoA

KM=1.3 mM for UDP-glucosamine

KM=2 mM for glucose-1-P

KM=3.7 mM for N-acetylgalactosamine-1-P

KM=15 mM for galactosamine-1-phosphate

Sequence caution

The sequence AAA62081.1 differs from that shown. Reason: Frameshift at position 179. Produces two ORFs.

The sequence AAA62082.1 differs from that shown. Reason: Frameshift at position 179. Produces two ORFs.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 456456Bifunctional protein GlmU HAMAP-Rule MF_01631
PRO_0000068701

Regions

Region1 – 229229Pyrophosphorylase HAMAP-Rule MF_01631
Region11 – 144UDP-GlcNAc binding HAMAP-Rule MF_01631
Region81 – 822UDP-GlcNAc binding HAMAP-Rule MF_01631
Region103 – 1053UDP-GlcNAc binding HAMAP-Rule MF_01631
Region230 – 25021Linker HAMAP-Rule MF_01631
Region251 – 456206N-acetyltransferase HAMAP-Rule MF_01631
Region386 – 3872Acetyl-CoA binding HAMAP-Rule MF_01631

Sites

Active site3631Proton acceptor By similarity
Metal binding1051Magnesium
Metal binding2271Magnesium
Binding site251UDP-GlcNAc By similarity
Binding site761UDP-GlcNAc
Binding site1401UDP-GlcNAc; via amide nitrogen
Binding site1541UDP-GlcNAc
Binding site1691UDP-GlcNAc
Binding site2271UDP-GlcNAc By similarity
Binding site3331UDP-GlcNAc
Binding site3511UDP-GlcNAc
Binding site3661UDP-GlcNAc
Binding site3771UDP-GlcNAc
Binding site3801Acetyl-CoA; via amide nitrogen
Binding site4051Acetyl-CoA
Binding site4231Acetyl-CoA; via amide nitrogen
Binding site4401Acetyl-CoA

Experimental info

Mutagenesis141G → A: 8-fold decrease in uridyltransferase activity. Creates steric conflict and decreases affinity for UTP. Ref.9
Mutagenesis181R → A: Dramatically impairs the uridyltransferase activity. Ref.9
Mutagenesis251K → A: 8-fold decrease in uridyltransferase activity. Ref.9
Mutagenesis2961C → A: No effect. Ref.8
Mutagenesis3071C → A: 1350-fold decrease in acetyltransferase activity. Ref.8
Mutagenesis3241C → A: 8-fold decrease in acetyltransferase activity. Ref.8
Mutagenesis3851C → A: No effect. Ref.8
Sequence conflict186 – 1872KL → NV in CAA25784. Ref.1

Secondary structure

............................................................................. 456
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0ACC7 [UniParc].

Last modified November 8, 2005. Version 1.
Checksum: 2F3C5C84F673C8A3

FASTA45649,190
        10         20         30         40         50         60 
MLNNAMSVVI LAAGKGTRMY SDLPKVLHTL AGKAMVQHVI DAANELGAAH VHLVYGHGGD 

        70         80         90        100        110        120 
LLKQALKDDN LNWVLQAEQL GTGHAMQQAA PFFADDEDIL MLYGDVPLIS VETLQRLRDA 

       130        140        150        160        170        180 
KPQGGIGLLT VKLDDPTGYG RITRENGKVT GIVEHKDATD EQRQIQEINT GILIANGADM 

       190        200        210        220        230        240 
KRWLAKLTNN NAQGEYYITD IIALAYQEGR EIVAVHPQRL SEVEGVNNRL QLSRLERVYQ 

       250        260        270        280        290        300 
SEQAEKLLLA GVMLRDPARF DLRGTLTHGR DVEIDTNVII EGNVTLGHRV KIGTGCVIKN 

       310        320        330        340        350        360 
SVIGDDCEIS PYTVVEDANL AAACTIGPFA RLRPGAELLE GAHVGNFVEM KKARLGKGSK 

       370        380        390        400        410        420 
AGHLTYLGDA EIGDNVNIGA GTITCNYDGA NKFKTIIGDD VFVGSDTQLV APVTVGKGAT 

       430        440        450 
IAAGTTVTRN VGENALAISR VPQTQKEGWR RPVKKK 

« Hide

References

« Hide 'large scale' references
[1]"DNA sequence around the Escherichia coli unc operon. Completion of the sequence of a 17 kilobase segment containing asnA, oriC, unc, glmS and phoS."
Walker J.E., Gay N.J., Saraste M., Eberle A.N.
Biochem. J. 224:799-815(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication."
Burland V.D., Plunkett G. III, Daniels D.L., Blattner F.R.
Genomics 16:551-561(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[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 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], SEQUENCE REVISION.
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]"Identification of the glmU gene encoding N-acetylglucosamine-1-phosphate uridyltransferase in Escherichia coli."
Mengin-Lecreulx D., van Heijenoort J.
J. Bacteriol. 175:6150-6157(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[6]"Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis."
Mengin-Lecreulx D., van Heijenoort J.
J. Bacteriol. 176:5788-5795(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[7]"Acetyltransfer precedes uridylyltransfer in the formation of UDP-N-acetylglucosamine in separable active sites of the bifunctional GlmU protein of Escherichia coli."
Gehring A.M., Lees W.J., Mindiola D.J., Walsh C.T., Brown E.D.
Biochemistry 35:579-585(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
[8]"Probing the role of cysteine residues in glucosamine-1-phosphate acetyltransferase activity of the bifunctional protein glmU from Escherichia coli: site-directed mutagenesis and characterization of the mutant enzymes."
Pompeo F., van Heijenoort J., Mengin-Lecreulx D.
J. Bacteriol. 180:4799-4803(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-296; CYS-307; CYS-324 AND CYS-385, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily."
Brown K., Pompeo F., Dixon S., Mengin-Lecreulx D., Cambillau C., Bourne Y.
EMBO J. 18:4096-4107(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF THE TRUNCATED FORM AND IN COMPLEX WITH UDP-GLCNAC, MUTAGENESIS OF GLY-14; ARG-18 AND LYS-25.
[10]"Structure of the Escherichia coli glmU pyrophosphorylase and acetyltransferase active sites."
Olsen L.R., Roderick S.L.
Biochemistry 40:1913-1921(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH UDP-GLCNAC AND COA, COFACTOR, SUBUNIT.
[11]"Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products."
Olsen L.R., Vetting M.W., Roderick S.L.
Protein Sci. 16:1230-1235(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH UDP-GLCNAC, COA AND MAGNESIUM IONS, SUBUNIT.
[12]"In vitro validation of acetyltransferase activity of GlmU as an antibacterial target in Haemophilus influenzae."
Buurman E.T., Andrews B., Gao N., Hu J., Keating T.A., Lahiri S., Otterbein L.R., Patten A.D., Stokes S.S., Shapiro A.B.
J. Biol. Chem. 286:40734-40742(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 233-452, ENZYME REGULATION, SUBUNIT.
[13]"Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series."
Green O.M., McKenzie A.R., Shapiro A.B., Otterbein L., Ni H., Patten A., Stokes S., Albert R., Kawatkar S., Breed J.
Bioorg. Med. Chem. Lett. 22:1510-1519(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 227-456, ENZYME REGULATION, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X01631 Genomic DNA. Translation: CAA25784.1.
L10328 Genomic DNA. Translation: AAA62082.1. Frameshift.
L10328 Genomic DNA. Translation: AAA62081.1. Frameshift.
U00096 Genomic DNA. Translation: AAC76753.1.
AP009048 Genomic DNA. Translation: BAE77558.1.
PIRC65176.
RefSeqNP_418186.1. NC_000913.3.
YP_491699.1. NC_007779.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FWYX-ray2.30A/B1-331[»]
1FXJX-ray2.25A/B1-331[»]
1HV9X-ray2.10A/B1-456[»]
2OI5X-ray2.25A/B1-456[»]
2OI6X-ray2.20A/B1-456[»]
2OI7X-ray2.54A/B1-456[»]
3TWDX-ray1.90A/B233-452[»]
4AA7X-ray2.00A/B227-456[»]
ProteinModelPortalP0ACC7.
SMRP0ACC7. Positions 3-451.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-31844N.
IntActP0ACC7. 19 interactions.
MINTMINT-1252604.
STRING511145.b3730.

Proteomic databases

PaxDbP0ACC7.
PRIDEP0ACC7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC76753; AAC76753; b3730.
BAE77558; BAE77558; BAE77558.
GeneID12933149.
948246.
KEGGecj:Y75_p3438.
eco:b3730.
PATRIC32122957. VBIEscCol129921_3854.

Organism-specific databases

EchoBASEEB1184.
EcoGeneEG11198. glmU.

Phylogenomic databases

eggNOGCOG1207.
HOGENOMHOG000283476.
KOK04042.
OMADCVTNQD.
OrthoDBEOG6Z6FQZ.
PhylomeDBP0ACC7.

Enzyme and pathway databases

BioCycEcoCyc:NAG1P-URIDYLTRANS-MONOMER.
ECOL316407:JW3708-MONOMER.
MetaCyc:NAG1P-URIDYLTRANS-MONOMER.
UniPathwayUPA00113; UER00532.
UPA00113; UER00533.
UPA00973.

Gene expression databases

GenevestigatorP0ACC7.

Family and domain databases

Gene3D3.90.550.10. 1 hit.
HAMAPMF_01631. GlmU.
InterProIPR005882. Bifunctional_GlmU.
IPR001451. Hexapep_transf.
IPR018357. Hexapep_transf_CS.
IPR025877. MobA-like_NTP_Trfase_dom.
IPR029044. Nucleotide-diphossugar_trans.
IPR011004. Trimer_LpxA-like.
[Graphical view]
PfamPF00132. Hexapep. 3 hits.
PF12804. NTP_transf_3. 1 hit.
[Graphical view]
SUPFAMSSF51161. SSF51161. 1 hit.
SSF53448. SSF53448. 1 hit.
TIGRFAMsTIGR01173. glmU. 1 hit.
PROSITEPS00101. HEXAPEP_TRANSFERASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP0ACC7.
PROP0ACC7.

Entry information

Entry nameGLMU_ECOLI
AccessionPrimary (citable) accession number: P0ACC7
Secondary accession number(s): P17114, P76746, Q2M848
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: November 8, 2005
Last modified: June 11, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene