PDBsum entry 2f00

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protein metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
476 a.a. *
_MG ×2
Waters ×378
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Escherichia coli murc
Structure: Udp-n-acetylmuramate--l-alanine ligase. Chain: a, b. Synonym: udp-n-acetylmuramoyl-l-alanine synthetase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: murc. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.217     R-free:   0.260
Authors: T.Deva,E.N.Baker,C.J.Squire,C.A.Smith
Key ref:
T.Deva et al. (2006). Structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC). Acta Crystallogr D Biol Crystallogr, 62, 1466-1474. PubMed id: 17139082 DOI: 10.1107/S0907444906038376
10-Nov-05     Release date:   24-Oct-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P17952  (MURC_ECOLI) -  UDP-N-acetylmuramate--L-alanine ligase
491 a.a.
476 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - UDP-N-acetylmuramate--L-alanine ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Peptidoglycan Biosynthesis (Part 1)
      Reaction: ATP + UDP-N-acetylmuramate + L-alanine = ADP + phosphate + UDP-N- acetylmuramoyl-L-alanine
+ UDP-N-acetylmuramate
+ L-alanine
+ phosphate
+ UDP-N- acetylmuramoyl-L-alanine
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     cell wall organization   6 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1107/S0907444906038376 Acta Crystallogr D Biol Crystallogr 62:1466-1474 (2006)
PubMed id: 17139082  
Structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC).
T.Deva, E.N.Baker, C.J.Squire, C.A.Smith.
The bacterial cell wall provides essential protection from the external environment and confers strength and rigidity to counteract internal osmotic pressure. Without this layer the cell would be easily ruptured and it is for this reason that biosynthetic pathways leading to the formation of peptidoglycan have for many years been a prime target for effective antibiotics. Central to this pathway are four similar ligase enzymes which add peptide groups to glycan moieties. As part of a program to better understand the structure-function relationships in these four enzymes, the crystal structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC) has been determined to 2.6 A resolution. The structure was solved by multiwavelength anomalous diffraction methods from a single selenomethionine-substituted crystal and refined to a crystallographic R factor of 0.212 (R(free) = 0.259). The enzyme has a modular multi-domain structure very similar to those of other members of the mur family of ATP-dependent amide-bond ligases. Detailed comparison of these four enzymes shows that considerable conformational changes are possible. These changes, together with the recruitment of two different N-terminal domains, allow this family of enzymes to bind a substrate which is identical at one end and at the other has the growing peptide tail which will ultimately become part of the rigid bacterial cell wall. Comparison of the E. coli and Haemophilus influenzae structures and analysis of the sequences of known MurC enzymes indicate the presence of a ;dimerization' motif in almost 50% of the MurC enzymes and points to a highly conserved loop in domain 3 that may play a key role in amino-acid ligand specificity.
  Selected figure(s)  
Figure 5.
Figure 5 Stereoview of the superposition of the P-loop in the four mur ligases. For clarity, only EcMurC strand 6 and helix 6 (blue) are shown. The residues comprising the P-loop are shown as coloured bonds for MurC (blue), MurD (green), MurE (red) and MurF (yellow).
Figure 6.
Figure 6 Relative positions of the substrates for MurC (UDPMurNAc; cyan), MurD (UDPMurNAc:L-Ala; magenta) and MurE (UDPMurNAc-tripeptide product; black) after superposition of the three structures based upon domain 2. Domains 2 and 3 for MurC are shown, but domain 1 is omitted for clarity. The bound nucleotide (AMPPNP) is shown in ball-and-stick representation and the approximate location of the terminal carboxylate group is indicated.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1466-1474) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
18974047 M.Fiuza, M.J.Canova, D.Patin, M.Letek, I.Zanella-Cléon, M.Becchi, L.M.Mateos, D.Mengin-Lecreulx, V.Molle, and J.A.Gil (2008).
The MurC Ligase Essential for Peptidoglycan Biosynthesis Is Regulated by the Serine/Threonine Protein Kinase PknA in Corynebacterium glutamicum.
  J Biol Chem, 283, 36553-36563.  
17608695 M.Ishibashi, K.Kurokawa, S.Nishida, K.Ueno, M.Matsuo, and K.Sekimizu (2007).
Isolation of temperature-sensitive mutations in murC of Staphylococcus aureus.
  FEMS Microbiol Lett, 274, 204-209.  
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.