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PDBsum entry 1uag

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Ligase PDB id
1uag
Jmol
Contents
Protein chain
428 a.a. *
Ligands
SO4 ×2
UMA
Waters ×294
* Residue conservation analysis
PDB id:
1uag
Name: Ligase
Title: Udp-n-acetylmuramoyl-l-alanine:d-glutamate ligase
Structure: Udp-n-acetylmuramoyl-l-alanine/:d-glutamate ligase. Chain: a. Synonym: murd. Engineered: yes. Other_details: udp-n-acetylmuramoyl-l-alanine bound, ph 7.2
Source: Escherichia coli. Organism_taxid: 562. Cell_line: jm83. Gene: murd gene. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.95Å     R-factor:   0.190     R-free:   0.235
Authors: J.Bertrand,E.Fanchon,O.Dideberg
Key ref:
J.A.Bertrand et al. (1997). Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli. EMBO J, 16, 3416-3425. PubMed id: 9218784 DOI: 10.1093/emboj/16.12.3416
Date:
13-Mar-97     Release date:   18-Mar-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P14900  (MURD_ECOLI) -  UDP-N-acetylmuramoylalanine--D-glutamate ligase
Seq:
Struc:
438 a.a.
428 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: ATP + UDP-N-acetylmuramoyl-L-alanine + glutamate = ADP + phosphate + UDP- N-acetylmuramoyl-L-alanyl-D-glutamate
ATP
+
UDP-N-acetylmuramoyl-L-alanine
Bound ligand (Het Group name = UMA)
corresponds exactly
+ glutamate
= ADP
+ phosphate
+ UDP- N-acetylmuramoyl-L-alanyl-D-glutamate
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     5 terms  

 

 
    reference    
 
 
DOI no: 10.1093/emboj/16.12.3416 EMBO J 16:3416-3425 (1997)
PubMed id: 9218784  
 
 
Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli.
J.A.Bertrand, G.Auger, E.Fanchon, L.Martin, D.Blanot, J.van Heijenoort, O.Dideberg.
 
  ABSTRACT  
 
UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) is a cytoplasmic enzyme involved in the biosynthesis of peptidoglycan which catalyzes the addition of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA). The crystal structure of MurD in the presence of its substrate UMA has been solved to 1.9 A resolution. Phase information was obtained from multiple anomalous dispersion using the K-shell edge of selenium in combination with multiple isomorphous replacement. The structure comprises three domains of topology each reminiscent of nucleotide-binding folds: the N- and C-terminal domains are consistent with the dinucleotide-binding fold called the Rossmann fold, and the central domain with the mononucleotide-binding fold also observed in the GTPase family. The structure reveals the binding site of the substrate UMA, and comparison with known NTP complexes allows the identification of residues interacting with ATP. The study describes the first structure of the UDP-N-acetylmuramoyl-peptide ligase family.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Ribbon diagram of the binary complex of MurD and UMA produced with the program Molscript (Kraulis, 1991). Domain 1 is shown in pink, domain 2 in blue, domain 3 in green and UMA in red. For reasons of continuity, the two missing loops in the structure, residues 221 -225 and 241 -244, are shown interconnected in the figure.
Figure 6.
Figure 6 Proposed catalytic mechanism for the formation of UDP-N-acetylmuramoyl-L-alanine-D-glutamate by MurD.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 3416-3425) copyright 1997.  
  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
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
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.  
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.  
17669425 B.Nocek, E.Evdokimova, M.Proudfoot, M.Kudritska, L.L.Grochowski, R.H.White, A.Savchenko, A.F.Yakunin, A.Edwards, and A.Joachimiak (2007).
Structure of an amide bond forming F(420):gamma-glutamyl ligase from Archaeoglobus fulgidus -- a member of a new family of non-ribosomal peptide synthases.
  J Mol Biol, 372, 456-469.
PDB codes: 2g9i 2phn
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.  
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
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
16436710 Y.Yang, A.Severin, R.Chopra, G.Krishnamurthy, G.Singh, W.Hu, D.Keeney, K.Svenson, P.J.Petersen, P.Labthavikul, D.M.Shlaes, B.A.Rasmussen, A.A.Failli, J.S.Shumsky, K.M.Kutterer, A.Gilbert, and T.S.Mansour (2006).
3,5-dioxopyrazolidines, novel inhibitors of UDP-N- acetylenolpyruvylglucosamine reductase (MurB) with activity against gram-positive bacteria.
  Antimicrob Agents Chemother, 50, 556-564.  
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.  
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
15562516 N.Rekha, S.M.Machado, C.Narayanan, A.Krupa, and N.Srinivasan (2005).
Interaction interfaces of protein domains are not topologically equivalent across families within superfamilies: Implications for metabolic and signaling pathways.
  Proteins, 58, 339-353.  
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
14500881 K.Matsuda, T.Nishioka, K.Kinoshita, T.Kawabata, and N.Go (2003).
Finding evolutionary relations beyond superfamilies: fold-based superfamilies.
  Protein Sci, 12, 2239-2251.  
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.  
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.  
11327854 T.E.Benson, M.S.Harris, G.H.Choi, J.I.Cialdella, J.T.Herberg, J.P.Martin, and E.T.Baldwin (2001).
A structural variation for MurB: X-ray crystal structure of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB).
  Biochemistry, 40, 2340-2350.
PDB code: 1hsk
11717264 V.Chazalet, K.Uehara, R.A.Geremia, and C.Breton (2001).
Identification of essential amino acids in the Azorhizobium caulinodans fucosyltransferase NodZ.
  J Bacteriol, 183, 7067-7075.  
10852860 C.Ma, and R.J.Redfield (2000).
Point mutations in a peptidoglycan biosynthesis gene cause competence induction in Haemophilus influenzae.
  J Bacteriol, 182, 3323-3330.  
10951215 H.Berg, K.Ziegler, K.Piotukh, K.Baier, W.Lockau, and R.Volkmer-Engert (2000).
Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers.
  Eur J Biochem, 267, 5561-5570.  
10841783 R.E.Campbell, S.C.Mosimann, I.van De Rijn, M.E.Tanner, and N.C.Strynadka (2000).
The first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation.
  Biochemistry, 39, 7012-7023.
PDB codes: 1dli 1dlj
  10892798 S.Ha, D.Walker, Y.Shi, and S.Walker (2000).
The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis.
  Protein Sci, 9, 1045-1052.
PDB code: 1f0k
10666581 Y.Yan, S.Munshi, Y.Li, K.A.Pryor, F.Marsilio, and B.Leiting (1999).
Crystallization and preliminary X-ray analysis of the Escherichia coli UDP-MurNAc-tripeptide D-alanyl-D-alanine-adding enzyme (MurF).
  Acta Crystallogr D Biol Crystallogr, 55, 2033-2034.  
9538689 O.Dideberg, and J.Bertrand (1998).
Tubulin tyrosine ligase: a shared fold with the glutathione synthetase ADP-forming family.
  Trends Biochem Sci, 23, 57-58.  
9843369 W.Wang, T.J.Kappock, J.Stubbe, and S.E.Ealick (1998).
X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli.
  Biochemistry, 37, 15647-15662.
PDB code: 1gso
9425668 J.Trias, and E.M.Gordon (1997).
Innovative approaches to novel antibacterial drug discovery.
  Curr Opin Biotechnol, 8, 757-762.  
  9416615 M.Y.Galperin, and E.V.Koonin (1997).
A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity.
  Protein Sci, 6, 2639-2643.  
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.