PDBsum entry 1p31

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
463 a.a. *
EPU ×2
_MG ×4
Waters ×700
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of udp-n-acetylmuramic acid:l-alanine liga from haemophilus influenzae
Structure: Udp-n-acetylmuramate--alanine ligase. Chain: a, b. Synonym: udp-n-acetylmuramoyl-l-alanine synthetase. Engineered: yes
Source: Haemophilus influenzae. Organism_taxid: 727. Gene: murc. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.85Å     R-factor:   0.171     R-free:   0.208
Authors: C.D.Mol,A.Brooun,D.R.Dougan,M.T.Hilgers,L.W.Tari,R.A.Wijnand M.W.Knuth,D.E.Mcree,R.V.Swanson
Key ref: C.D.Mol et al. (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. PubMed id: 12837790
16-Apr-03     Release date:   15-Jul-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P45066  (MURC_HAEIN) -  UDP-N-acetylmuramate--L-alanine ligase
475 a.a.
463 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
Bound ligand (Het Group name = EPU)
corresponds exactly
+ 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     4 terms  


J Bacteriol 185:4152-4162 (2003)
PubMed id: 12837790  
Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae.
C.D.Mol, A.Brooun, D.R.Dougan, M.T.Hilgers, L.W.Tari, R.A.Wijnands, M.W.Knuth, D.E.McRee, R.V.Swanson.
UDP-N-acetylmuramic acid:L-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg(2+) and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-L-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn(2+) have been determined to 1.85- and 1.7-A resolution, respectively. These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine. An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound. The MurC active site clearly shows that the gamma-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group. These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21445265 D.Das, M.Hervé, J.Feuerhelm, C.L.Farr, H.J.Chiu, M.A.Elsliger, M.W.Knuth, H.E.Klock, M.D.Miller, A.Godzik, S.A.Lesley, A.M.Deacon, D.Mengin-Lecreulx, and I.A.Wilson (2011).
Structure and function of the first full-length murein peptide ligase (Mpl) cell wall recycling protein.
  PLoS One, 6, e17624.
PDB code: 3hn7
20361049 J.O.Wrabl, and V.J.Hilser (2010).
Investigating homology between proteins using energetic profiles.
  PLoS Comput Biol, 6, e1000722.  
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.  
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.  
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.  
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.  
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.  
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.  
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
17012590 T.Hai, K.M.Frey, and A.Steinbüchel (2006).
Engineered cyanophycin synthetase (CphA) from Nostoc ellipsosporum confers enhanced CphA activity and cyanophycin accumulation to Escherichia coli.
  Appl Environ Microbiol, 72, 7652-7660.  
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
15146505 G.Spraggon, R.Schwarzenbacher, A.Kreusch, C.C.Lee, P.Abdubek, E.Ambing, T.Biorac, L.S.Brinen, J.M.Canaves, J.Cambell, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, S.Eshagi, R.Floyd, A.Godzik, C.Grittini, S.K.Grzechnik, E.Hampton, L.Jaroszewski, C.Karlak, H.E.Klock, E.Koesema, J.S.Kovarik, P.Kuhn, I.Levin, D.McMullan, T.M.McPhillips, M.D.Miller, A.Morse, K.Moy, J.Ouyang, R.Page, K.Quijano, A.Robb, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, F.von Delft, X.Wang, B.West, G.Wolf, Q.Xu, K.O.Hodgson, J.Wooley, S.A.Lesley, and I.A.Wilson (2004).
Crystal structure of an Udp-n-acetylmuramate-alanine ligase MurC (TM0231) from Thermotoga maritima at 2.3 A resolution.
  Proteins, 55, 1078-1081.
PDB code: 1j6u
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.