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PDBsum entry 2fu7
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2fu7

 

 

 

 

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Contents
Protein chains
266 a.a. *
Ligands
SO4 ×6
PHN ×2
GOL ×2
Metals
_CU ×6
Waters ×452
* Residue conservation analysis
PDB id:
2fu7
Name: Hydrolase
Title: Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (cu- substituted form)
Structure: Metallo-beta-lactamase l1. Chain: a, b. Synonym: beta-lactamase type ii, penicillinase. Engineered: yes
Source: Stenotrophomonas maltophilia. Organism_taxid: 40324. Strain: iid 1275. Cellular_location: periplasm. Gene: l1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.85Å     R-factor:   0.165     R-free:   0.195
Authors: L.Nauton,G.Garau,R.Kahn,O.Dideberg
Key ref:
L.Nauton et al. (2008). Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia. J Mol Biol, 375, 257-269. PubMed id: 17999929 DOI: 10.1016/j.jmb.2007.10.036
Date:
26-Jan-06     Release date:   30-Jan-07    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P52700  (BLA1_STEMA) -  Metallo-beta-lactamase L1 type 3 from Stenotrophomonas maltophilia
Seq:
Struc: 		290 a.a.
266 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.5.2.6  - beta-lactamase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Penicillin Biosynthesis and Metabolism
      Reaction: a beta-lactam + H2O = a substituted beta-amino acid
      Cofactor: Zn(2+)

 

 
DOI no: 10.1016/j.jmb.2007.10.036 J Mol Biol 375:257-269 (2008)
PubMed id: 17999929  
 
 
Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia.
L.Nauton, R.Kahn, G.Garau, J.F.Hernandez, O.Dideberg.
 
  ABSTRACT  
 
One mechanism by which bacteria can escape the action of beta-lactam antibiotics is the production of metallo-beta-lactamases. Inhibition of these enzymes should restore the action of these widely used antibiotics. The tetrameric enzyme L1 from Stenotrophomonas maltophilia was used as a model system to determine a series of high-resolution crystal structures of apo, mono and bi-metal substituted proteins as well as protein-inhibitor complexes. Unexpectedly, although the apo structure revealed only few significant structural differences from the holo structure, some inhibitors were shown to induce amino acid side-chain rotations in the tightly packed active site. Moreover, one inhibitor employs a new binding mode in order to interact with the di-zinc center. This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Chemical formulae of the substrate (Nitrocefin) and inhibitors used in this work. Major components of MBL inhibitors are colored: the zinc binding group (ZN-B), the hydrophobic extension (A–E) and the hydrophilic extension (B–E) in yellow, pink and green, respectively. 		Figure 3.
Figure 3. Stereo views showing the active site of L1 in the group I structures. Additional water molecules or sulfate ions are shown compared to Figure 2 when they are in the second shell of Zn coordination. Zn ligands and amino acid site-chains forming the active side are displayed. Metal and hydrogen bonds are in full and broken red lines, respectively. For clarity, zinc ligands and water molecule labels, and hydrogen bonds displayed in Figure 2 are not shown.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 375, 257-269) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20394454 C.Bebrone, P.Lassaux, L.Vercheval, J.S.Sohier, A.Jehaes, E.Sauvage, and M.Galleni (2010).
Current challenges in antimicrobial chemotherapy: focus on ß-lactamase inhibition.
  Drugs, 70, 651-679.  
20065329 S.M.Drawz, and R.A.Bonomo (2010).
Three decades of beta-lactamase inhibitors.
  Clin Microbiol Rev, 23, 160-201.  
19228020 Z.Hu, L.J.Spadafora, C.E.Hajdin, B.Bennett, and M.W.Crowder (2009).
Structure and mechanism of copper- and nickel-substituted analogues of metallo-beta-lactamase L1.
  Biochemistry, 48, 2981-2989.  
18627129 D.Liu, J.Momb, P.W.Thomas, A.Moulin, G.A.Petsko, W.Fast, and D.Ringe (2008).
Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis. 1. Product-bound structures.
  Biochemistry, 47, 7706-7714.
PDB codes: 3dha 3dhb 3dhc
18831550 Z.Hu, G.Periyannan, B.Bennett, and M.W.Crowder (2008).
Role of the Zn1 and Zn2 sites in metallo-beta-lactamase L1.
  J Am Chem Soc, 130, 14207-14216.  
18445468 Z.Hu, G.R.Periyannan, and M.W.Crowder (2008).
Folding strategy to prepare Co(II)-substituted metallo-beta-lactamase L1.
  Anal Biochem, 378, 177-183.  
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.

 

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