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PDBsum entry 2bmi

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
2bmi
Jmol
Contents
Protein chains
228 a.a. *
Metals
_NA ×2
_ZN ×4
Waters ×419
* Residue conservation analysis
PDB id:
2bmi
Name: Hydrolase
Title: Metallo-beta-lactamase
Structure: Protein (class b beta-lactamase). Chain: a, b. Synonym: beta-lactamase. Engineered: yes. Other_details: metallo-beta-lactamase, class b beta- lactamase
Source: Bacteroides fragilis. Organism_taxid: 817. Strain: bl21. Gene: ccra. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Not given
Resolution:
2.00Å     R-factor:   0.196     R-free:   0.262
Authors: A.Carfi,E.Duee,O.Dideberg
Key ref:
A.Carfi et al. (1998). X-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an orthorhombic crystal form. Acta Crystallogr D Biol Crystallogr, 54, 45-57. PubMed id: 9761816 DOI: 10.1107/S090744499700927X
Date:
17-Sep-98     Release date:   23-Sep-98    
Supersedes: 1bmi
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P25910  (BLAB_BACFG) -  Beta-lactamase type II
Seq:
Struc:
249 a.a.
228 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+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to antibiotic   2 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
DOI no: 10.1107/S090744499700927X Acta Crystallogr D Biol Crystallogr 54:45-57 (1998)
PubMed id: 9761816  
 
 
X-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an orthorhombic crystal form.
A.Carfi, E.Duée, R.Paul-Soto, M.Galleni, J.M.Frère, O.Dideberg.
 
  ABSTRACT  
 
beta-Lactamases are extracellular or periplasmic bacterial enzymes which confer resistance to beta-lactam antibiotics. On the basis of their catalytic mechanisms, they can be divided into two major groups: active-site serine enzymes (classes A, C and D) and the ZnII enzymes (class B). The first crystal structure of a class B enzyme, the metallo-beta-lactamase from Bacillus cereus, has been solved at 2.5 A resolution [Carfi, Pares, Duée, Galleni, Duez, Frère & Dideberg (1995). EMBO J. 14, 4914-4921]. Recently, the crystal structure of the metallo-beta-lactamase from Bacteroides fragilis has been determined in a tetragonal space group [Concha, Rasmussen, Bush & Herzberg (1996). Structure, 4, 823-836]. The structure of the metallo-beta-lactamase from B. fragilis in an orthorhombic crystal form at 2.0 A resolution is reported here. The final crystallographic R is 0.196 for all the 32501 observed reflections in the range 10-2.0 A. The refined model includes 458 residues, 437 water molecules, four zinc and two sodium ions. These structures are discussed with reference to Zn binding and activity. A catalytic mechanism is proposed which is coherent with metallo-beta-lactamases being active with either one Zn ion (as in Aeromonas hydrophila) or two Zn ions (as in B. fragilis) bound to the protein.
 
  Selected figure(s)  
 
Figure 4.
Stereoview of the superposition of the two independent molecules. Labels 1 and 2 refers to Zn1 and Zn2 (see text). The distance between the C [alpha] atoms of residues 31 and 176 varies from 14.2 to 12.9 between the open and closed form. [Figure 5]-[gr0735fig5thm.gif] Figure 5 Secondary structure and hydrogen bonding within the B. fragilis [beta] -lactamase structure. The diagram was prepared using the program HERA (Hutchinson & Thornton, 1990 [Hutchinson, E. G. & Thornton, J. M. (1990). Proteins, 8, 203-212.]-[bluearr.gif] ).
Figure 11.
Stereoview of the docking of [beta] -lactam substrates in the B. fragilis [beta] -lactamase active site. The substrates displayed in black are (a) ampicillin and (b) cephaloridine. The corresponding chemical structures are shown on the left side. Interactions used in the docking procedure (see text) are indicated with a dashed line.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1998, 54, 45-57) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20305272 Y.Yamaguchi, N.Takashio, J.Wachino, Y.Yamagata, Y.Arakawa, K.Matsuda, and H.Kurosaki (2010).
Structure of metallo-beta-lactamase IND-7 from a Chryseobacterium indologenes clinical isolate at 1.65-A resolution.
  J Biochem, 147, 905-915.
PDB code: 3l6n
19039608 F.R.Salsbury, M.W.Crowder, S.F.Kingsmore, and J.J.Huntley (2009).
Molecular dynamic simulations of the metallo-beta-lactamase from Bacteroides fragilis in the presence and absence of a tight-binding inhibitor.
  J Mol Model, 15, 133-145.  
18449576 A.Badarau, and M.I.Page (2008).
Loss of enzyme activity during turnover of the Bacillus cereus beta-lactamase catalysed hydrolysis of beta-lactams due to loss of zinc ion.
  J Biol Inorg Chem, 13, 919-928.  
18230049 V.Gupta (2008).
Metallo beta lactamases in Pseudomonas aeruginosa and Acinetobacter species.
  Expert Opin Investig Drugs, 17, 131-143.  
16406807 K.De Vriendt, G.Van Driessche, B.Devreese, C.Bebrone, C.Anne, J.M.Frère, M.Galleni, and J.Van Beeumen (2006).
Monitoring the zinc affinity of the metallo-beta-lactamase CphA by automated nanoESI-MS.
  J Am Soc Mass Spectrom, 17, 180-188.  
15831827 T.R.Walsh, M.A.Toleman, L.Poirel, and P.Nordmann (2005).
Metallo-beta-lactamases: the quiet before the storm?
  Clin Microbiol Rev, 18, 306-325.  
15215079 G.Garau, I.García-Sáez, C.Bebrone, C.Anne, P.Mercuri, M.Galleni, J.M.Frère, and O.Dideberg (2004).
Update of the standard numbering scheme for class B beta-lactamases.
  Antimicrob Agents Chemother, 48, 2347-2349.  
15461559 N.H.Georgopapadakou (2004).
Beta-lactamase inhibitors: evolving compounds for evolving resistance targets.
  Expert Opin Investig Drugs, 13, 1307-1318.  
12724330 C.Damblon, M.Jensen, A.Ababou, I.Barsukov, C.Papamicael, C.J.Schofield, L.Olsen, R.Bauer, and G.C.Roberts (2003).
The inhibitor thiomandelic acid binds to both metal ions in metallo-beta-lactamase and induces positive cooperativity in metal binding.
  J Biol Chem, 278, 29240-29251.  
12725860 C.Moali, C.Anne, J.Lamotte-Brasseur, S.Groslambert, B.Devreese, J.Van Beeumen, M.Galleni, and J.M.Frère (2003).
Analysis of the importance of the metallo-beta-lactamase active site loop in substrate binding and catalysis.
  Chem Biol, 10, 319-329.  
11940588 A.M.Simm, C.S.Higgins, A.L.Carenbauer, M.W.Crowder, J.H.Bateson, P.M.Bennett, A.R.Clarke, S.E.Halford, and T.R.Walsh (2002).
Characterization of monomeric L1 metallo-beta -lactamase and the role of the N-terminal extension in negative cooperativity and antibiotic hydrolysis.
  J Biol Chem, 277, 24744-24752.  
11714924 I.C.Materon, and T.Palzkill (2001).
Identification of residues critical for metallo-beta-lactamase function by codon randomization and selection.
  Protein Sci, 10, 2556-2565.  
11181339 M.Galleni, J.Lamotte-Brasseur, G.M.Rossolini, J.Spencer, O.Dideberg, and J.M.Frère (2001).
Standard numbering scheme for class B beta-lactamases.
  Antimicrob Agents Chemother, 45, 660-663.  
  10933508 L.Chantalat, E.Duée, M.Galleni, J.M.Frère, and O.Dideberg (2000).
Structural effects of the active site mutation cysteine to serine in Bacillus cereus zinc-beta-lactamase.
  Protein Sci, 9, 1402-1406.
PDB code: 1dxk
10508780 A.D.Cameron, M.Ridderström, B.Olin, and B.Mannervik (1999).
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.
  Structure, 7, 1067-1078.
PDB codes: 1qh3 1qh5
10508665 Z.Wang, W.Fast, A.M.Valentine, and S.J.Benkovic (1999).
Metallo-beta-lactamase: structure and mechanism.
  Curr Opin Chem Biol, 3, 614-622.  
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.