spacer
spacer

PDBsum entry 1e8c
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Ligase PDB id
1e8c

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
496 a.a. *
Ligands
UAG-API ×2
Metals
_CL
Waters ×393
* Residue conservation analysis
PDB id:
1e8c
Name: Ligase
Title: Structure of mure the udp-n-acetylmuramyl tripeptide synthetase from e. Coli
Structure: Udp-n-acetylmuramoylalanyl-d-glutamate--2,6-diaminopimelate ligase. Chain: a, b. Engineered: yes. Other_details: udp-n-acetylmuramyl-tripeptide bound in active site
Source: Escherichia coli. Organism_taxid: 562. Gene: mure. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.00Å     R-factor:   0.202     R-free:   0.230
Authors: E.J.Gordon,L.Chantala,O.Dideberg
Key ref:
E.Gordon et al. (2001). Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli. J Biol Chem, 276, 10999-11006. PubMed id: 11124264 DOI: 10.1074/jbc.M009835200
Date:
19-Sep-00     Release date:   13-Sep-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P22188  (MURE_ECOLI) -  UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase from Escherichia coli (strain K12)
Seq:
Struc: 		495 a.a.
496 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.6.3.2.13  - UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Peptidoglycan Biosynthesis (Part 1)
      Reaction: UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + meso-2,6- diaminopimelate + ATP = UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gamma-D- glutamyl-meso-2,6-diaminopimelate + ADP + phosphate + H+
UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate
 +
meso-2,6- diaminopimelate
Bound ligand (Het Group name = API)
corresponds exactly 		+ ATP
 = UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gamma-D- glutamyl-meso-2,6-diaminopimelate
 + ADP
 + phosphate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M009835200 J Biol Chem 276:10999-11006 (2001)
PubMed id: 11124264  
 
 
Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli.
E.Gordon, B.Flouret, L.Chantalat, J.van Heijenoort, D.Mengin-Lecreulx, O.Dideberg.
 
  ABSTRACT  
 
UDP-N-acetylmuramoyl-l-alanyl-d-glutamate:meso-diaminopimelate ligase is a cytoplasmic enzyme that catalyzes the addition of meso-diaminopimelic acid to nucleotide precursor UDP-N-acetylmuramoyl-l-alanyl-d-glutamate in the biosynthesis of bacterial cell-wall peptidoglycan. The crystal structure of the Escherichia coli enzyme in the presence of the final product of the enzymatic reaction, UDP-MurNAc-l-Ala-gamma-d-Glu-meso-A(2)pm, has been solved to 2.0 A resolution. Phase information was obtained by multiwavelength anomalous dispersion using the K shell edge of selenium. The protein consists of three domains, two of which have a topology reminiscent of the equivalent domain found in the already established three-dimensional structure of the UDP-N-acetylmuramoyl-l-alanine: D-glutamate-ligase (MurD) ligase, which catalyzes the immediate previous step of incorporation of d-glutamic acid in the biosynthesis of the peptidoglycan precursor. The refined model reveals the binding site for UDP-MurNAc-l-Ala-gamma-d-Glu-meso-A(2)pm, and comparison with the six known MurD structures allowed the identification of residues involved in the enzymatic mechanism. Interestingly, during refinement, an excess of electron density was observed, leading to the conclusion that, as in MurD, a carbamylated lysine residue is present in the active site. In addition, the structural determinant responsible for the selection of the amino acid to be added to the nucleotide precursor was identified.
 
  Selected figure(s)  
 
Figure 5.
Fig. 5. Schematic drawing of the UMT binding in molecule B. For clarity, only hydrogen bond interactions are shown. 		Figure 8.
Fig. 8. Interaction of the A[2]pm moiety of UMT with MurE. Only side chains involved in hydrogen bonds are shown. The green line represents the loop between 19 and 14.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 10999-11006) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21153518 C.Basavannacharya, P.R.Moody, T.Munshi, N.Cronin, N.H.Keep, and S.Bhakta (2010).
Essential residues for the enzyme activity of ATP-dependent MurE ligase from Mycobacterium tuberculosis.
  Protein Cell, 1, 1011-1022.
PDB code: 2xja
20179338 T.C.Terwilliger (2010).
Rapid model building of alpha-helices in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 268-275.  
20179339 T.C.Terwilliger (2010).
Rapid model building of beta-sheets in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 276-284.  
20179340 T.C.Terwilliger (2010).
Rapid chain tracing of polypeptide backbones in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 285-294.  
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.  
20567260 W.Zhao, Y.Zhong, H.Yuan, J.Wang, H.Zheng, Y.Wang, X.Cen, F.Xu, J.Bai, X.Han, G.Lu, Y.Zhu, Z.Shao, H.Yan, C.Li, N.Peng, Z.Zhang, Y.Zhang, W.Lin, Y.Fan, Z.Qin, Y.Hu, B.Zhu, S.Wang, X.Ding, and G.P.Zhao (2010).
Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism.
  Cell Res, 20, 1096-1108.  
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.  
19820100 D.Patin, J.Bostock, D.Blanot, D.Mengin-Lecreulx, and I.Chopra (2009).
Functional and biochemical analysis of the Chlamydia trachomatis ligase MurE.
  J Bacteriol, 191, 7430-7435.  
19465773 T.C.Terwilliger, P.D.Adams, R.J.Read, A.J.McCoy, N.W.Moriarty, R.W.Grosse-Kunstleve, P.V.Afonine, P.H.Zwart, and L.W.Hung (2009).
Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard.
  Acta Crystallogr D Biol Crystallogr, 65, 582-601.  
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.  
18315498 L.E.Zawadzke, M.Norcia, C.R.Desbonnet, H.Wang, K.Freeman-Cook, and T.J.Dougherty (2008).
Identification of an inhibitor of the MurC enzyme, which catalyzes an essential step in the peptidoglycan precursor synthesis pathway.
  Assay Drug Dev Technol, 6, 95.  
18036201 M.Garcia, F.Myouga, K.Takechi, H.Sato, K.Nabeshima, N.Nagata, S.Takio, K.Shinozaki, and H.Takano (2008).
An Arabidopsis homolog of the bacterial peptidoglycan synthesis enzyme MurE has an essential role in chloroplast development.
  Plant J, 53, 924-934.  
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.  
17335103 K.Strancar, A.Boniface, D.Blanot, and S.Gobec (2007).
Phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: L-lysine ligase (MurE).
  Arch Pharm (Weinheim), 340, 127-134.  
17384195 M.Hervé, A.Boniface, S.Gobec, D.Blanot, and D.Mengin-Lecreulx (2007).
Biochemical characterization and physiological properties of Escherichia coli UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase.
  J Bacteriol, 189, 3987-3995.  
17120230 M.K.Kim, M.K.Cho, H.E.Song, D.Kim, B.H.Park, J.H.Lee, G.B.Kang, S.H.Kim, Y.J.Im, D.S.Lee, and S.H.Eom (2007).
Crystal structure of UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from Thermus caldophilus.
  Proteins, 66, 751-754.
PDB codes: 2gqt 2gqu
16492149 G.F.Stamper, K.L.Longenecker, E.H.Fry, C.G.Jakob, A.S.Florjancic, Y.G.Gu, D.D.Anderson, C.S.Cooper, T.Zhang, R.F.Clark, Y.Cia, C.L.Black-Schaefer, J.Owen McCall, C.G.Lerner, P.J.Hajduk, B.A.Beutel, and V.S.Stoll (2006).
Structure-based optimization of MurF inhibitors.
  Chem Biol Drug Des, 67, 58-65.  
17158705 J.Deutscher, C.Francke, and P.W.Postma (2006).
How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria.
  Microbiol Mol Biol Rev, 70, 939.  
17139082 T.Deva, E.N.Baker, C.J.Squire, and C.A.Smith (2006).
Structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC).
  Acta Crystallogr D Biol Crystallogr, 62, 1466-1474.
PDB code: 2f00
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
16318626 K.M.Mayer, S.R.McCorkle, and J.Shanklin (2005).
Linking enzyme sequence to function using Conserved Property Difference Locator to identify and annotate positions likely to control specific functionality.
  BMC Bioinformatics, 6, 284.  
14747725 A.M.Blewett, A.J.Lloyd, A.Echalier, V.Fülöp, C.G.Dowson, T.D.Bugg, and D.I.Roper (2004).
Expression, purification, crystallization and preliminary characterization of uridine 5'-diphospho-N-acetylmuramoyl L-alanyl-D-glutamate:lysine ligase (MurE) from Streptococcus pneumoniae 110K/70.
  Acta Crystallogr D Biol Crystallogr, 60, 359-361.  
14962386 S.Biarrotte-Sorin, A.P.Maillard, J.Delettré, W.Sougakoff, M.Arthur, and C.Mayer (2004).
Crystal structures of Weissella viridescens FemX and its complex with UDP-MurNAc-pentapeptide: insights into FemABX family substrates recognition.
  Structure, 12, 257-267.
PDB codes: 1ne9 1p4n
12492849 A.El Zoeiby, F.Sanschagrin, and R.C.Levesque (2003).
Structure and function of the Mur enzymes: development of novel inhibitors.
  Mol Microbiol, 47, 1.  
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
12837773 S.Nessler, S.Fieulaine, S.Poncet, A.Galinier, J.Deutscher, and J.Janin (2003).
HPr kinase/phosphorylase, the sensor enzyme of catabolite repression in Gram-positive bacteria: structural aspects of the enzyme and the complex with its protein substrate.
  J Bacteriol, 185, 4003-4010.  
12832760 T.C.Terwilliger (2003).
Improving macromolecular atomic models at moderate resolution by automated iterative model building, statistical density modification and refinement.
  Acta Crystallogr D Biol Crystallogr, 59, 1174-1182.  
14501107 T.C.Terwilliger (2003).
Statistical density modification using local pattern matching.
  Acta Crystallogr D Biol Crystallogr, 59, 1688-1701.  
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.  
12000608 I.Chopra, L.Hesse, and A.J.O'Neill (2002).
Exploiting current understanding of antibiotic action for discovery of new drugs.
  J Appl Microbiol, 92, 4S.  
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.

 

spacer
spacer