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PDBsum entry 2yz3
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2yz3

 

 

 

 

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Contents
Protein chains
225 a.a. *
Ligands
SO4 ×4
M5P ×2
Metals
_ZN ×4
Waters ×212
* Residue conservation analysis
PDB id:
2yz3
Name: Hydrolase
Title: Crystallographic investigation of inhibition mode of the vim-2 metallo-beta-lactamase from pseudomonas aeruginosa with mercaptocarboxylate inhibitor
Structure: Metallo-beta-lactamase. Chain: a, b. Synonym: vim-2, metallo-beta-lactamase vim-2, vim-2 beta-lactamase. Engineered: yes
Source: Pseudomonas putida. Organism_taxid: 303. Gene: vim-2, bla vim-2, blavim-2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.212     R-free:   0.247
Authors: Y.Yamaguchi,Y.Yamagata,Y.Arakawa,H.Kurosaki
Key ref: Y.Yamaguchi et al. (2007). Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor. J Med Chem, 50, 6647-6653. PubMed id: 18052313
Date:
02-May-07     Release date:   11-Mar-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q7BJM5  (Q7BJM5_PSEPU) -  VIM-2 from Pseudomonas putida
Seq:
Struc: 		266 a.a.
225 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+)

 

 
J Med Chem 50:6647-6653 (2007)
PubMed id: 18052313  
 
 
Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor.
Y.Yamaguchi, W.Jin, K.Matsunaga, S.Ikemizu, Y.Yamagata, J.Wachino, N.Shibata, Y.Arakawa, H.Kurosaki.
 
  ABSTRACT  
 
The VIM-2 metallo-beta-lactamase enzyme from Pseudomonas aeruginosa catalyzes the hydrolysis of most beta-lactam antibiotics including carbapenems, and there are currently no potent inhibitors of such enzymes. We found rac-2-omega-phenylpropyl-3-mercaptopropionic acid, phenylC3SH, to be a potent inhibitor of VIM-2. The structure of the VIM-2-phenylC3SH complex was determined by X-ray crystallography to 2.3 A. The structure revealed that the thiol group of phenylC3SH bridged to the two zinc(II) ions and the phenyl group interacted with Tyr67(47) on loop1 near the active site, by pi-pi stacking interactions. The methylene group interacted with Phe61(42) located at the bottom of loop1 through CH-pi interactions. Dynamic movements were observed in Arg228(185) and Asn233(190) on loop2, compared with the native structure (PDB code: 1KO3 ). These results suggest that the above-mentioned four residues play important roles in the binding and recognition of inhibitors or substrates and in stabilizing a loop in the VIM-2 enzyme.
 

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.  
20564281 G.De Pascale, and G.D.Wright (2010).
Antibiotic resistance by enzyme inactivation: from mechanisms to solutions.
  Chembiochem, 11, 1325-1334.  
20498317 L.Borgianni, J.Vandenameele, A.Matagne, L.Bini, R.A.Bonomo, J.M.Frère, G.M.Rossolini, and J.D.Docquier (2010).
Mutational analysis of VIM-2 reveals an essential determinant for metallo-beta-lactamase stability and folding.
  Antimicrob Agents Chemother, 54, 3197-3204.  
20624761 M.Merino, F.J.Pérez-Llarena, F.Kerff, M.Poza, S.Mallo, S.Rumbo-Feal, A.Beceiro, C.Juan, A.Oliver, and G.Bou (2010).
Role of changes in the L3 loop of the active site in the evolution of enzymatic activity of VIM-type metallo-beta-lactamases.
  J Antimicrob Chemother, 65, 1950-1954.  
20121112 P.Oelschlaeger, N.Ai, K.T.Duprez, W.J.Welsh, and J.H.Toney (2010).
Evolving carbapenemases: can medicinal chemists advance one step ahead of the coming storm?
  J Med Chem, 53, 3013-3027.  
20065329 S.M.Drawz, and R.A.Bonomo (2010).
Three decades of beta-lactamase inhibitors.
  Clin Microbiol Rev, 23, 160-201.  
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
19553129 D.Minond, S.A.Saldanha, P.Subramaniam, M.Spaargaren, T.Spicer, J.R.Fotsing, T.Weide, V.V.Fokin, K.B.Sharpless, M.Galleni, C.Bebrone, P.Lassaux, and P.Hodder (2009).
Inhibitors of VIM-2 by screening pharmacologically active and click-chemistry compound libraries.
  Bioorg Med Chem, 17, 5027-5037.  
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.

 

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