PDBsum entry 1hv9

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
449 a.a. *
COA ×2
UD1 ×2
_CO ×5
Waters ×257
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of e. Coli glmu: analysis of pyrophosphorylase and acetyltransferase active sites
Structure: Udp-n-acetylglucosamine pyrophosphorylase. Chain: a, b. Synonym: n-acetylglucosamine-1-phosphate uridyltransferase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: glmu. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Trimer (from PDB file)
2.10Å     R-factor:   0.211     R-free:   0.248
Authors: L.R.Olsen,S.L.Roderick
Key ref:
L.R.Olsen and S.L.Roderick (2001). Structure of the Escherichia coli GlmU pyrophosphorylase and acetyltransferase active sites. Biochemistry, 40, 1913-1921. PubMed id: 11329257 DOI: 10.1021/bi002503n
08-Jan-01     Release date:   21-Feb-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0ACC7  (GLMU_ECOLI) -  Bifunctional protein GlmU
456 a.a.
449 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Glucosamine-1-phosphate N-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

UDP-N-acetylglucosamine Biosynthesis
      Reaction: Acetyl-CoA + alpha-D-glucosamine 1-phosphate = CoA + N-acetyl-alpha-D- glucosamine 1-phosphate
+ alpha-D-glucosamine 1-phosphate
Bound ligand (Het Group name = COA)
corresponds exactly
N-acetyl-alpha-D- glucosamine 1-phosphate
Bound ligand (Het Group name = UD1)
matches with 48.72% similarity
   Enzyme class 2: E.C.  - UDP-N-acetylglucosamine diphosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: UTP + N-acetyl-alpha-D-glucosamine 1-phosphate = diphosphate + UDP-N- acetyl-alpha-D-glucosamine
+ N-acetyl-alpha-D-glucosamine 1-phosphate
= diphosphate
+ UDP-N- acetyl-alpha-D-glucosamine
Bound ligand (Het Group name = UD1)
corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   8 terms 
  Biochemical function     catalytic activity     9 terms  


DOI no: 10.1021/bi002503n Biochemistry 40:1913-1921 (2001)
PubMed id: 11329257  
Structure of the Escherichia coli GlmU pyrophosphorylase and acetyltransferase active sites.
L.R.Olsen, S.L.Roderick.
N-Acetylglucosamine-1-PO(4) uridyltransferase (GlmU) is a trimeric bifunctional enzyme that catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-GlcNAc. The X-ray crystal structure of Escherichia coli GlmU in complex with UDP-GlcNAc and CoA has been determined to 2.1 A resolution and reveals a two-domain architecture that is responsible for these two reactions. The C-terminal domain is responsible for the CoA-dependent acetylation of Glc-1-PO(4) to GlcNAc-1-PO(4) and displays the longest left-handed parallel beta-helix observed to date. The acetyltransferase active site defined by the binding site for CoA makes use of residues from all three subunits and is positioned beneath an open cavity large enough to accommodate the Glc-1-PO(4) acetyl acceptor. The N-terminal domain catalyzes uridyl transfer from UTP to GlcNAc-1-PO(4) to form the final products UDP-GlcNAc and pyrophosphate. This domain is composed of a central seven-stranded beta-sheet surrounded by six alpha-helices in a Rossmann fold-like topology. A Co(2+) ion binds to just one of the two independent pyrophosphorylase active sites present in the crystals studied here, each of which nonetheless binds UDP-GlcNAc. The conformational changes of the enzyme and sugar nucleotide that accompany metal binding may provide a window into the structural dynamics that accompany catalysis.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21370307 J.F.Trempe, S.Shenker, G.Kozlov, and K.Gehring (2011).
Self-association studies of the bifunctional N-acetylglucosamine-1-phosphate uridyltransferase from Escherichia coli.
  Protein Sci, 20, 745-752.  
20571117 B.Sagot, M.Gaysinski, M.Mehiri, J.M.Guigonis, D.Le Rudulier, and G.Alloing (2010).
Osmotically induced synthesis of the dipeptide N-acetylglutaminylglutamine amide is mediated by a new pathway conserved among bacteria.
  Proc Natl Acad Sci U S A, 107, 12652-12657.  
20224564 G.Zhao, W.Guan, L.Cai, and P.G.Wang (2010).
Enzymatic route to preparative-scale synthesis of UDP-GlcNAc/GalNAc, their analogues and GDP-fucose.
  Nat Protoc, 5, 636-646.  
20832292 H.M.Holden, P.D.Cook, and J.B.Thoden (2010).
Biosynthetic enzymes of unusual microbial sugars.
  Curr Opin Struct Biol, 20, 543-550.  
20400541 Z.Zhang, J.Akutsu, and Y.Kawarabayasi (2010).
Identification of novel acetyltransferase activity on the thermostable protein ST0452 from Sulfolobus tokodaii strain 7.
  J Bacteriol, 192, 3287-3293.  
18986988 A.K.Bergfeld, H.Claus, N.K.Lorenzen, F.Spielmann, U.Vogel, and M.Mühlenhoff (2009).
The Polysialic Acid-specific O-Acetyltransferase OatC from Neisseria meningitidis Serogroup C Evolved Apart from Other Bacterial Sialate O-Acetyltransferases.
  J Biol Chem, 284, 6.  
19655786 C.M.Bartling, and C.R.Raetz (2009).
Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis.
  Biochemistry, 48, 8672-8683.
PDB code: 3eh0
19349513 M.P.Pereira, J.E.Blanchard, C.Murphy, S.L.Roderick, and E.D.Brown (2009).
High-throughput screening identifies novel inhibitors of the acetyltransferase activity of Escherichia coli GlmU.
  Antimicrob Agents Chemother, 53, 2306-2311.  
  19407371 S.K.Verma, M.Jaiswal, N.Kumar, A.Parikh, V.K.Nandicoori, and B.Prakash (2009).
Structure of N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) from Mycobacterium tuberculosis in a cubic space group.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 435-439.
PDB code: 3foq
19237750 Z.Zhang, E.M.Bulloch, R.D.Bunker, E.N.Baker, and C.J.Squire (2009).
Structure and function of GlmU from Mycobacterium tuberculosis.
  Acta Crystallogr D Biol Crystallogr, 65, 275-283.
PDB codes: 2qkx 3d8v 3d98
18627619 C.J.Zea, G.Camci-Unal, and N.L.Pohl (2008).
Thermodynamics of binding of divalent magnesium and manganese to uridine phosphates: implications for diabetes-related hypomagnesaemia and carbohydrate biocatalysis.
  Chem Cent J, 2, 15.  
18266853 H.Barreteau, A.Kovac, A.Boniface, M.Sova, S.Gobec, and D.Blanot (2008).
Cytoplasmic steps of peptidoglycan biosynthesis.
  FEMS Microbiol Rev, 32, 168-207.  
18218712 I.Mochalkin, S.Lightle, L.Narasimhan, D.Bornemeier, M.Melnick, S.Vanderroest, and L.McDowell (2008).
Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site.
  Protein Sci, 17, 577-582.
PDB code: 2vd4
18398908 J.H.Choi, C.Govaerts, B.C.May, and F.E.Cohen (2008).
Analysis of the sequence and structural features of the left-handed beta-helical fold.
  Proteins, 73, 150-160.  
  18765909 J.Yin, C.R.Garen, M.M.Cherney, L.T.Cherney, and M.N.James (2008).
Expression, purification and preliminary crystallographic analysis of N-acetylglucosamine-1-phosphate uridylyltransferase from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 805-808.  
18573680 W.Zhang, V.C.Jones, M.S.Scherman, S.Mahapatra, D.Crick, S.Bhamidi, Y.Xin, M.R.McNeil, and Y.Ma (2008).
Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase.
  Int J Biochem Cell Biol, 40, 2560-2571.  
17698807 A.H.Williams, and C.R.Raetz (2007).
Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase.
  Proc Natl Acad Sci U S A, 104, 13543-13550.
PDB codes: 2qia 2qiv
17519228 A.K.Bergfeld, H.Claus, U.Vogel, and M.Mühlenhoff (2007).
Biochemical characterization of the polysialic acid-specific O-acetyltransferase NeuO of Escherichia coli K1.
  J Biol Chem, 282, 22217-22227.  
17392279 D.Maruyama, Y.Nishitani, T.Nonaka, A.Kita, T.A.Fukami, T.Mio, H.Yamada-Okabe, T.Yamada-Okabe, and K.Miki (2007).
Crystal structure of uridine-diphospho-N-acetylglucosamine pyrophosphorylase from Candida albicans and catalytic reaction mechanism.
  J Biol Chem, 282, 17221-17230.
PDB codes: 2yqc 2yqh 2yqj 2yqs
18029420 I.Mochalkin, S.Lightle, Y.Zhu, J.F.Ohren, C.Spessard, N.Y.Chirgadze, C.Banotai, M.Melnick, and L.McDowell (2007).
Characterization of substrate binding and catalysis in the potential antibacterial target N-acetylglucosamine-1-phosphate uridyltransferase (GlmU).
  Protein Sci, 16, 2657-2666.
PDB codes: 2v0h 2v0i 2v0j 2v0k 2v0l
17473010 L.R.Olsen, M.W.Vetting, and S.L.Roderick (2007).
Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products.
  Protein Sci, 16, 1230-1235.
PDB codes: 2oi5 2oi6 2oi7
17303565 T.Steiner, A.C.Lamerz, P.Hess, C.Breithaupt, S.Krapp, G.Bourenkov, R.Huber, R.Gerardy-Schahn, and U.Jacob (2007).
Open and closed structures of the UDP-glucose pyrophosphorylase from Leishmania major.
  J Biol Chem, 282, 13003-13010.
PDB codes: 2oef 2oeg
16835299 A.H.Williams, R.M.Immormino, D.T.Gewirth, and C.R.Raetz (2006).
Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide.
  Proc Natl Acad Sci U S A, 103, 10877-10882.
PDB code: 2aq9
  17142897 D.Maruyama, Y.Nishitani, T.Nonaka, A.Kita, T.A.Fukami, T.Mio, H.Yamada-Okabe, T.Yamada-Okabe, and K.Miki (2006).
Purification, crystallization and preliminary X-ray diffraction studies of UDP-N-acetylglucosamine pyrophosphorylase from Candida albicans.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1206-1208.  
16408321 S.Milewski, I.Gabriel, and J.Olchowy (2006).
Enzymes of UDP-GlcNAc biosynthesis in yeast.
  Yeast, 23, 1.  
16102001 C.Q.Wenzel, C.Daniels, R.A.Keates, D.Brewer, and J.S.Lam (2005).
Evidence that WbpD is an N-acetyltransferase belonging to the hexapeptide acyltransferase superfamily and an important protein for O-antigen biosynthesis in Pseudomonas aeruginosa PAO1.
  Mol Microbiol, 57, 1288-1303.  
  16511013 J.R.Cupp-Vickery, R.Y.Igarashi, and C.R.Meyer (2005).
Preliminary crystallographic analysis of ADP-glucose pyrophosphorylase from Agrobacterium tumefaciens.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 266-268.  
16169849 M.T.Mok, and M.R.Edwards (2005).
Kinetic and physical characterization of the inducible UDP-N-acetylglucosamine pyrophosphorylase from Giardia intestinalis.
  J Biol Chem, 280, 39363-39372.  
15692569 X.Jin, M.A.Ballicora, J.Preiss, and J.H.Geiger (2005).
Crystal structure of potato tuber ADP-glucose pyrophosphorylase.
  EMBO J, 24, 694-704.
PDB codes: 1yp2 1yp3 1yp4
14718535 A.J.Davis, M.A.Perugini, B.J.Smith, J.D.Stewart, T.Ilg, A.N.Hodder, and E.Handman (2004).
Properties of GDP-mannose pyrophosphorylase, a critical enzyme and drug target in Leishmania mexicana.
  J Biol Chem, 279, 12462-12468.  
15044493 C.R.Sweet, A.H.Williams, M.J.Karbarz, C.Werts, S.R.Kalb, R.J.Cotter, and C.R.Raetz (2004).
Enzymatic synthesis of lipid A molecules with four amide-linked acyl chains. LpxA acyltransferases selective for an analog of UDP-N-acetylglucosamine in which an amine replaces the 3"-hydroxyl group.
  J Biol Chem, 279, 25411-25419.  
12740380 A.Pfoestl, A.Hofinger, P.Kosma, and P.Messner (2003).
Biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-galactose in Aneurinibacillus thermoaerophilus L420-91T.
  J Biol Chem, 278, 26410-26417.  
12581308 J.B.Frueauf, M.A.Ballicora, and J.Preiss (2003).
ADP-glucose pyrophosphorylase from potato tuber: site-directed mutagenesis of homologous aspartic acid residues in the small and large subunits.
  Plant J, 33, 503-511.  
12824488 J.Liu, and A.Mushegian (2003).
Three monophyletic superfamilies account for the majority of the known glycosyltransferases.
  Protein Sci, 12, 1418-1431.  
12771141 L.E.Kehoe, J.Snidwongse, P.Courvalin, J.B.Rafferty, and I.A.Murray (2003).
Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens.
  J Biol Chem, 278, 29963-29970.
PDB codes: 1mr7 1mr9 1mrl
12794190 M.A.Ballicora, A.A.Iglesias, and J.Preiss (2003).
ADP-glucose pyrophosphorylase, a regulatory enzyme for bacterial glycogen synthesis.
  Microbiol Mol Biol Rev, 67, 213.  
12045108 C.R.Raetz, and C.Whitfield (2002).
Lipopolysaccharide endotoxins.
  Annu Rev Biochem, 71, 635-700.  
11901475 D.W.Green (2002).
The bacterial cell wall as a source of antibacterial targets.
  Expert Opin Ther Targets, 6, 1.  
12171937 J.Sivaraman, V.Sauvé, A.Matte, and M.Cygler (2002).
Crystal structure of Escherichia coli glucose-1-phosphate thymidylyltransferase (RffH) complexed with dTTP and Mg2+.
  J Biol Chem, 277, 44214-44219.
PDB code: 1mc3
11910040 T.W.Beaman, K.W.Vogel, D.G.Drueckhammer, J.S.Blanchard, and S.L.Roderick (2002).
Acyl group specificity at the active site of tetrahydridipicolinate N-succinyltransferase.
  Protein Sci, 11, 974-979.
PDB codes: 1kgq 1kgt
11937062 X.G.Wang, L.R.Olsen, and S.L.Roderick (2002).
Structure of the lac operon galactoside acetyltransferase.
  Structure, 10, 581-588.
PDB codes: 1kqa 1krr 1kru 1krv
11707391 C.Peneff, P.Ferrari, V.Charrier, Y.Taburet, C.Monnier, V.Zamboni, J.Winter, M.Harnois, F.Fassy, and Y.Bourne (2001).
Crystal structures of two human pyrophosphorylase isoforms in complexes with UDPGlc(Gal)NAc: role of the alternatively spliced insert in the enzyme oligomeric assembly and active site architecture.
  EMBO J, 20, 6191-6202.
PDB codes: 1jv1 1jv3 1jvd 1jvg
11717516 L.Lo Leggio, F.Dal Degan, P.Poulsen, S.O.Sørensen, K.Harlow, P.Harris, and S.Larsen (2001).
Crystallization and preliminary X-ray analysis of maltose O-acetyltransferase.
  Acta Crystallogr D Biol Crystallogr, 57, 1915-1918.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.