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PDBsum entry 1eeh
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Ligase PDB id
1eeh

 

 

 

 

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Contents
Protein chain
431 a.a. *
Ligands
UMA
Waters ×186
* Residue conservation analysis
PDB id:
1eeh
Name: Ligase
Title: Udp-n-acetylmuramoyl-l-alanine:d-glutamate ligase
Structure: Udp-n-acetylmuramoyl-l-alanine:d-glutamate ligase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.219     R-free:   0.265
Authors: J.A.Bertrand,E.Fanchon,L.Martin,L.Chantalat,G.Auger,D.Blanot,J.Van Heijenoort,O.Dideberg
Key ref:
J.A.Bertrand et al. (2000). "Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase. J Mol Biol, 301, 1257-1266. PubMed id: 10966819 DOI: 10.1006/jmbi.2000.3994
Date:
31-Jan-00     Release date:   17-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P14900  (MURD_ECOLI) -  UDP-N-acetylmuramoylalanine--D-glutamate ligase from Escherichia coli (strain K12)
Seq:
Struc: 		438 a.a.
431 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.3.2.9  - UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Peptidoglycan Biosynthesis (Part 1)
      Reaction: UDP-N-acetyl-alpha-D-muramoyl-L-alanine + D-glutamate + ATP = UDP-N- acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + ADP + phosphate + H+
UDP-N-acetyl-alpha-D-muramoyl-L-alanine
 + D-glutamate
 + ATP
 = UDP-N- acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate
Bound ligand (Het Group name = UMA)
matches with 43.40% similarity 		+ ADP
 + phosphate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2000.3994 J Mol Biol 301:1257-1266 (2000)
PubMed id: 10966819  
 
 
"Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.
J.A.Bertrand, E.Fanchon, L.Martin, L.Chantalat, G.Auger, D.Blanot, J.van Heijenoort, O.Dideberg.
 
  ABSTRACT  
 
UDP-N-acetylmuramoyl-l-alanine:d-glutamate (MurD) ligase catalyses the addition of d-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-l-alanine (UMA). The crystal structures of Escherichia coli in the substrate-free form and MurD complexed with UMA have been determined at 2.4 A and 1.88 A resolution, respectively. The MurD structure comprises three domains each of a topology reminiscent of nucleotide-binding folds. In the two structures the C-terminal domain undergoes a large rigid-body rotation away from the N-terminal and central domains. These two "open" structures were compared with the four published "closed" structures of MurD. In addition the comparison reveals which regions are affected by the binding of UMA, ATP and d-Glu. Also we compare and discuss two structurally characterized enzymes which belong to the same ligase superfamily: MurD and folylpolyglutamate synthetase (FGS). The analysis allows the identification of key residues involved in the reaction mechanism of FGS. The determination of the two "open" conformation structures represents a new step towards the complete elucidation of the enzymatic mechanism of the MurD ligase.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Stereo view showing the "closed" form model of FGS (black) superimposed on the central and C-terminal domains of MurD.UMA.ADP.Mg2+ (green). The Image -Ala of UMA is shown in red and ADP in blue. 		Figure 6.
Figure 6. Stereo view of the active-site region of the "closed" conformation of FGS. Residues that play a role in the binding of either ADP.Mg2+ and/or the terminal carboxylate group of UMA are labelled. The carboxylate group of UMA is shown in orange, ADP in deep blue, water molecules in red and Mg2+ in black. The blue lines show strand b6, the P-loop and the beginning of helix a6.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 301, 1257-1266) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21524830 I.Sosič, H.Barreteau, M.Simčič, R.Sink, J.Cesar, A.Zega, S.G.Grdadolnik, C.Contreras-Martel, A.Dessen, A.Amoroso, B.Joris, D.Blanot, and S.Gobec (2011).
Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid.
  Eur J Med Chem, 46, 2880-2894.
PDB code: 2xpc
20024979 T.Tomasić, N.Zidar, A.Kovac, S.Turk, M.Simcic, D.Blanot, M.Müller-Premru, M.Filipic, S.G.Grdadolnik, A.Zega, M.Anderluh, S.Gobec, D.Kikelj, and L.Peterlin Masic (2010).
5-Benzylidenethiazolidin-4-ones as multitarget inhibitors of bacterial Mur ligases.
  ChemMedChem, 5, 286-295.  
18704940 A.Perdih, M.Hodoscek, and T.Solmajer (2009).
MurD ligase from E. coli: Tetrahedral intermediate formation study by hybrid quantum mechanical/molecular mechanical replica path method.
  Proteins, 74, 744-759.  
19198900 A.Perdih, U.Bren, and T.Solmajer (2009).
Binding free energy calculations of N-sulphonyl-glutamic acid inhibitors of MurD ligase.
  J Mol Model, 15, 983-996.  
19400768 C.Paradis-Bleau, A.Lloyd, F.Sanschagrin, H.Maaroufi, T.Clarke, A.Blewett, C.Dowson, D.I.Roper, T.D.Bugg, and R.C.Levesque (2009).
Pseudomonas aeruginosa MurE amide ligase: enzyme kinetics and peptide inhibitor.
  Biochem J, 421, 263-272.  
19099588 C.Paradis-Bleau, A.Lloyd, F.Sanschagrin, T.Clarke, A.Blewett, T.D.Bugg, and R.C.Levesque (2008).
Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF.
  BMC Biochem, 9, 33.  
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.  
18506905 T.Bratkovic, M.Lunder, U.Urleb, and B.Strukelj (2008).
Peptide inhibitors of MurD and MurE, essential enzymes of bacterial cell wall biosynthesis.
  J Basic Microbiol, 48, 202-206.  
17427948 A.Perdih, M.Kotnik, M.Hodoscek, and T.Solmajer (2007).
Targeted molecular dynamics simulation studies of binding and conformational changes in E. coli MurD.
  Proteins, 68, 243-254.  
17390395 G.Füser, and A.Steinbüchel (2007).
Analysis of genome sequences for genes of cyanophycin metabolism: identifying putative cyanophycin metabolizing prokaryotes.
  Macromol Biosci, 7, 278-296.  
16322581 K.L.Longenecker, G.F.Stamper, P.J.Hajduk, E.H.Fry, C.G.Jakob, J.E.Harlan, R.Edalji, D.M.Bartley, K.A.Walter, L.R.Solomon, T.F.Holzman, Y.G.Gu, C.G.Lerner, B.A.Beutel, and V.S.Stoll (2005).
Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure.
  Protein Sci, 14, 3039-3047.
PDB codes: 2am1 2am2
15705579 M.Mathieu, G.Debousker, S.Vincent, F.Viviani, N.Bamas-Jacques, and V.Mikol (2005).
Escherichia coli FolC structure reveals an unexpected dihydrofolate binding site providing an attractive target for anti-microbial therapy.
  J Biol Chem, 280, 18916-18922.
PDB codes: 1w78 1w7k
12837790 C.D.Mol, A.Brooun, D.R.Dougan, M.T.Hilgers, L.W.Tari, R.A.Wijnands, M.W.Knuth, D.E.McRee, and R.V.Swanson (2003).
Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae.
  J Bacteriol, 185, 4152-4162.
PDB codes: 1p31 1p3d
12909715 H.Li, H.Xu, D.E.Graham, and R.H.White (2003).
Glutathione synthetase homologs encode alpha-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses.
  Proc Natl Acad Sci U S A, 100, 9785-9790.  
12876369 T.Deva, K.D.Pryor, B.Leiting, E.N.Baker, and C.A.Smith (2003).
Purification, crystallization and preliminary X-ray analysis of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC).
  Acta Crystallogr D Biol Crystallogr, 59, 1510-1513.  
11901475 D.W.Green (2002).
The bacterial cell wall as a source of antibacterial targets.
  Expert Opin Ther Targets, 6, 1.  
11751809 Y.Urushibata, S.Tokuyama, and Y.Tahara (2002).
Characterization of the Bacillus subtilis ywsC gene, involved in gamma-polyglutamic acid production.
  J Bacteriol, 184, 337-343.  
11722566 S.Dementin, A.Bouhss, G.Auger, C.Parquet, D.Mengin-Lecreulx, O.Dideberg, J.van Heijenoort, and D.Blanot (2001).
Evidence of a functional requirement for a carbamoylated lysine residue in MurD, MurE and MurF synthetases as established by chemical rescue experiments.
  Eur J Biochem, 268, 5800-5807.  
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.

 

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