PDBsum entry 1j3g

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protein metals links
Hydrolase PDB id
Protein chain
187 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Solution structure of citrobacter freundii ampd
Structure: Ampd protein. Chain: a. Synonym: ampd. Engineered: yes
Source: Citrobacter freundii. Organism_taxid: 546. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: E.Liepinsh,C.Genereux,D.Dehareng,B.Joris,G.Otting
Key ref:
E.Liepinsh et al. (2003). NMR structure of Citrobacter freundii AmpD, comparison with bacteriophage T7 lysozyme and homology with PGRP domains. J Mol Biol, 327, 833-842. PubMed id: 12654266 DOI: 10.1016/S0022-2836(03)00185-2
31-Jan-03     Release date:   18-Feb-03    
Supersedes: 1j2s
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P82974  (AMPD_CITFR) -  1,6-anhydro-N-acetylmuramyl-L-alanine amidase AmpD
187 a.a.
187 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - N-acetylmuramoyl-L-alanine amidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in certain bacterial cell-wall glycopeptides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     peptidoglycan catabolic process   1 term 
  Biochemical function     hydrolase activity     3 terms  


DOI no: 10.1016/S0022-2836(03)00185-2 J Mol Biol 327:833-842 (2003)
PubMed id: 12654266  
NMR structure of Citrobacter freundii AmpD, comparison with bacteriophage T7 lysozyme and homology with PGRP domains.
E.Liepinsh, C.Généreux, D.Dehareng, B.Joris, G.Otting.
AmpD is a bacterial amidase involved in the recycling of cell-wall fragments in Gram-negative bacteria. Inactivation of AmpD leads to derepression of beta-lactamase expression, presenting a major pathway for the acquisition of constitutive antibiotic resistance. Here, we report the NMR structure of AmpD from Citrobacter freundii (PDB accession code 1J3G). A deep substrate-binding pocket explains the observed specificity for low molecular mass substrates. The fold is related to that of bacteriophage T7 lysozyme. Both proteins bind zinc at a conserved site and require zinc for amidase activity, although the enzymatic mechanism seems to differ in detail. The structure-based sequence alignment identifies conserved features that are also conserved in the eukaryotic peptidoglycan recognition protein (PGRP) domains, including the zinc-coordination site in several of them. PGRP domains thus belong to the same fold family and, where zinc-binding residues are conserved, may have amidase activity. This hypothesis is supported by the observation that human serum N-acetylmuramyl-L-alanine amidase seems to be identical with a soluble form of human PGRP-L.
  Selected figure(s)  
Figure 1.
Figure 1. Solution structure of AmpD and comparison with T7 lysozyme. (a) Ribbon representation of AmpD. The b-strands and a-helices are numbered as in Figure 2. White and yellow numbers distinguish strands and helices, respectively. The zinc ion is shown in purple. (b) Ribbon representation of T7 lysozyme (PDB code 1LBA). Second- ary-structure elements homologous to AmpD are coloured as in (a). (c) Stereo view of AmpD, showing a superposition of the backbone atoms in the 20 conformers representing the NMR structure (Table 1), in the same orientation as in (a). Numbers identify sequence positions. (d) Stereo view of the AmpD conformer closest to the mean structure of the 20 conformers shown in (c), using a heavy-atom representation in the same orientation as in (c). The polypeptide back- bone is drawn in green. The following colors were used for the side-chains: blue, Arg, Lys, positively charged His; red, Glu, Asp; yellow, Ala, Cys, Ile, Leu, Met, Phe, Pro, Trp, Val; gray, Asn, Gln, Ser, Thr, Tyr, uncharged His. The zinc ion is shown as a purple sphere, with the side-chains of the coordinating residues His34, His154 and Asp164 drawn in bold. Black spheres mark the C a positions of those residues, where point mutations have been found in con- stituitively b-lactamase expressing bacteria. 17
Figure 3.
Figure 3. Model of the AmpD-substrate complex. The solvent-accessible surface is shown with the following color code for different chemical groups: yellow, hydro- phobic; gray, hydrophilic; red, negatively charged; blue, positively charged. The zinc atom is displayed as a pur- ple sphere. The side-chains of the Zn 2+ -coordinating resi- dues and of Tyr63 were excluded from the surface calculation and drawn with green lines instead. The sub- strate, 1,6-anhydro MurNAc-L-alanyl-g-D-glutamyl-meso- diaminopimelic acid, is drawn in a line representation (blue) with carbonyl and carboxyl bonds in red.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 833-842) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20195500 N.Nikoh, J.P.McCutcheon, T.Kudo, S.Y.Miyagishima, N.A.Moran, and A.Nakabachi (2010).
Bacterial genes in the aphid genome: absence of functional gene transfer from Buchnera to its host.
  PLoS Genet, 6, e1000827.  
19237650 A.Pennartz, C.Généreux, C.Parquet, D.Mengin-Lecreulx, and B.Joris (2009).
Substrate-induced inactivation of the Escherichia coli AmiD N-acetylmuramoyl-L-alanine amidase highlights a new strategy to inhibit this class of enzyme.
  Antimicrob Agents Chemother, 53, 2991-2997.  
18535144 J.T.Park, and T.Uehara (2008).
How bacteria consume their own exoskeletons (turnover and recycling of cell wall peptidoglycan).
  Microbiol Mol Biol Rev, 72, 211.  
18266855 W.Vollmer, B.Joris, P.Charlier, and S.Foster (2008).
Bacterial peptidoglycan (murein) hydrolases.
  FEMS Microbiol Rev, 32, 259-286.  
17888003 M.Firczuk, and M.Bochtler (2007).
Folds and activities of peptidoglycan amidases.
  FEMS Microbiol Rev, 31, 676-691.  
17526703 T.Uehara, and J.T.Park (2007).
An anhydro-N-acetylmuramyl-L-alanine amidase with broad specificity tethered to the outer membrane of Escherichia coli.
  J Bacteriol, 189, 5634-5641.  
16723562 A.J.Schmidtke, and N.D.Hanson (2006).
Model system to evaluate the effect of ampD mutations on AmpC-mediated beta-lactam resistance.
  Antimicrob Agents Chemother, 50, 2030-2037.  
16548881 V.B.Pinheiro, and D.J.Ellar (2006).
How to kill a mocking bug?
  Cell Microbiol, 8, 545-557.  
16103125 L.Y.Low, C.Yang, M.Perego, A.Osterman, and R.C.Liddington (2005).
Structure and lytic activity of a Bacillus anthracis prophage endolysin.
  J Biol Chem, 280, 35433-35439.
PDB codes: 1yb0 2ar3
15361936 C.I.Chang, S.Pili-Floury, M.Hervé, C.Parquet, Y.Chelliah, B.Lemaitre, D.Mengin-Lecreulx, and J.Deisenhofer (2004).
A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity.
  PLoS Biol, 2, E277.
PDB code: 1s2j
14751763 D.Ferrandon, J.L.Imler, and J.A.Hoffmann (2004).
Sensing infection in Drosophila: Toll and beyond.
  Semin Immunol, 16, 43-53.  
15199960 G.K.Christophides, D.Vlachou, and F.C.Kafatos (2004).
Comparative and functional genomics of the innate immune system in the malaria vector Anopheles gambiae.
  Immunol Rev, 198, 127-148.  
15247237 J.Varea, B.Monterroso, J.L.Sáiz, C.López-Zumel, J.L.García, J.Laynez, P.García, and M.Menéndez (2004).
Structural and thermodynamic characterization of Pal, a phage natural chimeric lysin active against pneumococci.
  J Biol Chem, 279, 43697-43707.  
15044722 M.Bochtler, S.G.Odintsov, M.Marcyjaniak, and I.Sabala (2004).
Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases.
  Protein Sci, 13, 854-861.  
14603309 J.A.Hoffmann (2003).
The immune response of Drosophila.
  Nature, 426, 33-38.  
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 codes are shown on the right.