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Hydrolase PDB id
1a7t
Jmol
Contents
Protein chains
227 a.a. *
Ligands
MES ×2
Metals
_ZN ×4
_NA ×2
Waters ×337
* Residue conservation analysis
PDB id:
1a7t
Name: Hydrolase
Title: Metallo-beta-lactamase with mes
Structure: Metallo-beta-lactamase. Chain: a, b. Synonym: class b beta-lactamase. Engineered: yes. Mutation: yes
Source: Bacteroides fragilis. Organism_taxid: 817. Strain: tal3636. Variant: clinical isolate. Gene: ccra. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.85Å     R-factor:   0.151    
Authors: P.M.D.Fitzgerald,J.K.Wu,J.H.Toney
Key ref:
P.M.Fitzgerald et al. (1998). Unanticipated inhibition of the metallo-beta-lactamase from Bacteroides fragilis by 4-morpholineethanesulfonic acid (MES): a crystallographic study at 1.85-A resolution. Biochemistry, 37, 6791-6800. PubMed id: 9578564 DOI: 10.1021/bi9730339
Date:
17-Mar-98     Release date:   17-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P25910  (BLAB_BACFR) -  Beta-lactamase type II
Seq:
Struc: 		249 a.a.
227 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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: Zinc
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to antibiotic   2 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
DOI no: 10.1021/bi9730339 Biochemistry 37:6791-6800 (1998)
PubMed id: 9578564  
 
 
Unanticipated inhibition of the metallo-beta-lactamase from Bacteroides fragilis by 4-morpholineethanesulfonic acid (MES): a crystallographic study at 1.85-A resolution.
P.M.Fitzgerald, J.K.Wu, J.H.Toney.
 
  ABSTRACT  
 
As part of a structure-aided effort to design clinically useful inhibitors of metallo-beta-lactamases, the X-ray crystal structure of a complex between the metallo-beta-lactamase from Bacteroides fragilis and 4-morpholinoethanesulfonic acid (MES) has been determined and a model for the structure has been refined to a crystallographic R-factor of 0.151 for data between 10.0- and 1.85-A resolution. Although the binding of MES was an adventitious result of the use of MES as a buffer in the crystallization mixture, MES was subsequently shown to be a competitive inhibitor of the enzyme, with a Ki of 23 +/- 5 mM. MES binds in the same fashion to both of the molecules in the crystallographic asymmetric unit; both direct and solvent-mediated hydrogen bonds to the protein and to the binuclear zinc cluster are observed, involving the oxygens of the sulfonic acid group and the nitrogen of the morpholino ring. In addition, there are hydrophobic interactions between the morpholino ring and residues in the flexible beta-strand of the enzyme between residues 26 and 36. Comparison of this structure with the previously reported unliganded structures of the same enzyme [Concha, N. O., Rasmussen, B. A., Bush, K., and Herzberg, O. (1996) Structure 4, 823-836; Carfi, A., Duée, E., Paul-Soto, R., Galleni, M., Frère, reveals that although the overall conservation of structure in the three different crystal lattices is very high, binding of MES is correlated with a significant change in the conformation of this beta-strand. The flexibility of this beta-strand will be an important consideration in the design of inhibitors of the metallo-beta-lactamases.
 

Literature references that cite this PDB file's key reference

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The 1.5-A structure of Chryseobacterium meningosepticum zinc beta-lactamase in complex with the inhibitor, D-captopril.
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PDB code: 1m2x
12824483 J.J.Huntley, W.Fast, S.J.Benkovic, P.E.Wright, and H.J.Dyson (2003).
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PDB codes: 1oyx 1oz2 1oz3
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11847294 C.M.Gomes, C.Frazão, A.V.Xavier, J.Legall, and M.Teixeira (2002).
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Modeling of the metallo-beta-lactamase from B. fragilis: structural and dynamic effects of inhibitor binding.
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Identification of residues critical for metallo-beta-lactamase function by codon randomization and selection.
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Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases.
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PDB codes: 1e5r 1e5s
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.
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11327823 W.Fast, Z.Wang, and S.J.Benkovic (2001).
Familial mutations and zinc stoichiometry determine the rate-limiting step of nitrocefin hydrolysis by metallo-beta-lactamase from Bacteroides fragilis.
  Biochemistry, 40, 1640-1650.  
11063572 J.J.Huntley, S.D.Scrofani, M.J.Osborne, P.E.Wright, and H.J.Dyson (2000).
Dynamics of the metallo-beta-lactamase from Bacteroides fragilis in the presence and absence of a tight-binding inhibitor.
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  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
11498375 M.G.Page (2000).
b-Lactamase inhibitors.
  Drug Resist Updat, 3, 109-125.  
10757977 N.O.Concha, C.A.Janson, P.Rowling, S.Pearson, C.A.Cheever, B.P.Clarke, C.Lewis, M.Galleni, J.M.Frère, D.J.Payne, J.H.Bateson, and S.S.Abdel-Meguid (2000).
Crystal structure of the IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor.
  Biochemistry, 39, 4288-4298.
PDB codes: 1dd6 1ddk
10952572 S.Haruta, H.Yamaguchi, E.T.Yamamoto, Y.Eriguchi, M.Nukaga, K.O'Hara, and T.Sawai (2000).
Functional analysis of the active site of a metallo-beta-lactamase proliferating in Japan.
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  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
10498206 M.L.Greenlee, J.B.Laub, J.M.Balkovec, M.L.Hammond, G.G.Hammond, D.L.Pompliano, and J.H.Epstein-Toney (1999).
Synthesis and SAR of thioester and thiol inhibitors of IMP-1 metallo-beta-lactamase.
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  10508031 R.Nagano, Y.Adachi, H.Imamura, K.Yamada, T.Hashizume, and H.Morishima (1999).
Carbapenem derivatives as potential inhibitors of various beta-lactamases, including class B metallo-beta-lactamases.
  Antimicrob Agents Chemother, 43, 2497-2503.  
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.  
  9545432 J.H.Toney, P.M.Fitzgerald, N.Grover-Sharma, S.H.Olson, W.J.May, J.G.Sundelof, D.E.Vanderwall, K.A.Cleary, S.K.Grant, J.K.Wu, J.W.Kozarich, D.L.Pompliano, and G.G.Hammond (1998).
Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase.
  Chem Biol, 5, 185-196.
PDB code: 1a8t
  10066532 K.Bush, and G.H.Miller (1998).
Bacterial enzymatic resistance: beta-lactamases and aminoglycoside-modifying enzymes.
  Curr Opin Microbiol, 1, 509-515.  
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.