spacer
spacer

PDBsum entry 1e4d

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Beta-lactamase PDB id
1e4d
Jmol
Contents
Protein chains
243 a.a. *
Ligands
SO4 ×16
EDO ×6
Waters ×943
* Residue conservation analysis
PDB id:
1e4d
Name: Beta-lactamase
Title: Structure of oxa10 beta-lactamase at ph 8.3
Structure: Beta-lactamase oxa-10. Chain: a, b, c, d. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
1.8Å     R-factor:   0.198     R-free:   0.242
Authors: L.Maveyraud,D.Golemi,L.P.Kotra,S.Tranier,S.Vakulenko, S.Mobashery,J.P.Samama
Key ref:
L.Maveyraud et al. (2000). Insights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa. Structure, 8, 1289-1298. PubMed id: 11188693 DOI: 10.1016/S0969-2126(00)00534-7
Date:
03-Jul-00     Release date:   12-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P14489  (BLO10_PSEAI) -  Beta-lactamase OXA-10
Seq:
Struc:
266 a.a.
243 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     3 terms  

 

 
DOI no: 10.1016/S0969-2126(00)00534-7 Structure 8:1289-1298 (2000)
PubMed id: 11188693  
 
 
Insights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa.
L.Maveyraud, D.Golemi, L.P.Kotra, S.Tranier, S.Vakulenko, S.Mobashery, J.P.Samama.
 
  ABSTRACT  
 
BACKGROUND: beta-lactam antibiotic therapies are commonly challenged by the hydrolytic activities of beta-lactamases in bacteria. These enzymes have been grouped into four classes: A, B, C, and D. Class B beta-lactamases are zinc dependent, and enzymes of classes A, C, and D are transiently acylated on a serine residue in the course of the turnover chemistry. While class A and C beta-lactamases have been extensively characterized by biochemical and structural methods, class D enzymes remain the least studied despite their increasing importance in the clinic. RESULTS: The crystal structure of the OXA10 class D beta-lactamase has been solved to 1.66 A resolution from a gold derivative and MAD phasing. This structure reveals that beta-lactamases from classes D and A, despite very poor sequence similarity, share a similar overall fold. An additional beta strand in OXA10 mediates the association into dimers characterized by analytical ultracentrifugation. Major differences are found when comparing the molecular details of the active site of this class D enzyme to the corresponding regions in class A and C beta-lactamases. In the native structure of the OXA10 enzyme solved to 1.8 A, Lys-70 is carbamylated. CONCLUSIONS: Several features were revealed by this study: the dimeric structure of the OXA10 beta-lactamase, an extension of the substrate binding site which suggests that class D enzymes may bind other substrates beside beta-lactams, and carbamylation of the active site Lys-70 residue. The CO2-dependent activity of the OXA10 enzyme and the kinetic properties of the natural OXA17 mutant protein suggest possible relationships between carbamylation, inhibition of the enzyme by anions, and biphasic behavior of the enzyme.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Active Sites of Class D and Class A EnzymesDetailed view of the active site of OXA10 (top) and TEM-1 (bottom) in the same orientation. Main chain atoms are represented with bold lines, hydrogen bonds with hatched lines, and water molecules as dots

 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1289-1298) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20564281 G.De Pascale, and G.D.Wright (2010).
Antibiotic resistance by enzyme inactivation: from mechanisms to solutions.
  Chembiochem, 11, 1325-1334.  
20145076 J.D.Docquier, M.Benvenuti, V.Calderone, F.Giuliani, D.Kapetis, F.De Luca, G.M.Rossolini, and S.Mangani (2010).
Crystal structure of the narrow-spectrum OXA-46 class D beta-lactamase: relationship between active-site lysine carbamylation and inhibition by polycarboxylates.
  Antimicrob Agents Chemother, 54, 2167-2174.
PDB code: 3if6
21108605 L.Vercheval, C.Bauvois, A.di Paolo, F.Borel, J.L.Ferrer, E.Sauvage, A.Matagne, J.M.Frère, P.Charlier, M.Galleni, and F.Kerff (2010).
Three factors that modulate the activity of class D β-lactamases and interfere with the post-translational carboxylation of Lys70.
  Biochem J, 432, 495-504.
PDB codes: 2wgv 2wgw 2wkh 2wki
20086146 S.M.Drawz, C.R.Bethel, V.R.Doppalapudi, A.Sheri, S.R.Pagadala, A.M.Hujer, M.J.Skalweit, V.E.Anderson, S.G.Chen, J.D.Buynak, and R.A.Bonomo (2010).
Penicillin sulfone inhibitors of class D beta-lactamases.
  Antimicrob Agents Chemother, 54, 1414-1424.  
20065329 S.M.Drawz, and R.A.Bonomo (2010).
Three decades of beta-lactamase inhibitors.
  Clin Microbiol Rev, 23, 160-201.  
19863801 C.Ramel, M.Tobler, M.Meyer, L.Bigler, M.O.Ebert, B.Schellenberg, and R.Dudler (2009).
Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate.
  BMC Biochem, 10, 26.  
19485421 K.D.Schneider, C.R.Bethel, A.M.Distler, A.M.Hujer, R.A.Bonomo, and D.A.Leonard (2009).
Mutation of the active site carboxy-lysine (K70) of OXA-1 beta-lactamase results in a deacylation-deficient enzyme.
  Biochemistry, 48, 6136-6145.  
18559643 C.R.Bethel, A.M.Distler, M.W.Ruszczycky, M.P.Carey, P.R.Carey, A.M.Hujer, M.Taracila, M.S.Helfand, J.M.Thomson, M.Kalp, V.E.Anderson, D.A.Leonard, K.M.Hujer, T.Abe, A.M.Venkatesan, T.S.Mansour, and R.A.Bonomo (2008).
Inhibition of OXA-1 beta-lactamase by penems.
  Antimicrob Agents Chemother, 52, 3135-3143.  
18362192 Y.Doi, L.Poirel, D.L.Paterson, and P.Nordmann (2008).
Characterization of a naturally occurring class D beta-lactamase from Achromobacter xylosoxidans.
  Antimicrob Agents Chemother, 52, 1952-1956.  
17374723 E.Santillana, A.Beceiro, G.Bou, and A.Romero (2007).
Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis.
  Proc Natl Acad Sci U S A, 104, 5354-5359.
PDB code: 2jc7
16189095 C.Héritier, L.Poirel, P.E.Fournier, J.M.Claverie, D.Raoult, and P.Nordmann (2005).
Characterization of the naturally occurring oxacillinase of Acinetobacter baumannii.
  Antimicrob Agents Chemother, 49, 4174-4179.  
16262787 C.V.Gallant, C.Daniels, J.M.Leung, A.S.Ghosh, K.D.Young, L.P.Kotra, and L.L.Burrows (2005).
Common beta-lactamases inhibit bacterial biofilm formation.
  Mol Microbiol, 58, 1012-1024.  
15855521 F.Giuliani, J.D.Docquier, M.L.Riccio, L.Pagani, and G.M.Rossolini (2005).
OXA-46, a new class D beta-lactamase of narrow substrate specificity encoded by a blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate.
  Antimicrob Agents Chemother, 49, 1973-1980.  
16121396 J.Li, J.B.Cross, T.Vreven, S.O.Meroueh, S.Mobashery, and H.B.Schlegel (2005).
Lysine carboxylation in proteins: OXA-10 beta-lactamase.
  Proteins, 61, 246-257.  
16189136 S.A.Adediran, M.Nukaga, S.Baurin, J.M.Frère, and R.F.Pratt (2005).
Inhibition of class D beta-lactamases by acyl phosphates and phosphonates.
  Antimicrob Agents Chemother, 49, 4410-4412.  
15155197 D.Girlich, T.Naas, and P.Nordmann (2004).
Biochemical characterization of the naturally occurring oxacillinase OXA-50 of Pseudomonas aeruginosa.
  Antimicrob Agents Chemother, 48, 2043-2048.  
15504844 D.Girlich, T.Naas, and P.Nordmann (2004).
OXA-60, a chromosomal, inducible, and imipenem-hydrolyzing class D beta-lactamase from Ralstonia pickettii.
  Antimicrob Agents Chemother, 48, 4217-4225.  
15105882 J.Walther-Rasmussen, and N.Høiby (2004).
Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum beta-lactamases.
  Can J Microbiol, 50, 137-165.  
15461559 N.H.Georgopapadakou (2004).
Beta-lactamase inhibitors: evolving compounds for evolving resistance targets.
  Expert Opin Investig Drugs, 13, 1307-1318.  
12591921 D.Golemi-Kotra, J.Y.Cha, S.O.Meroueh, S.B.Vakulenko, and S.Mobashery (2003).
Resistance to beta-lactam antibiotics and its mediation by the sensor domain of the transmembrane BlaR signaling pathway in Staphylococcus aureus.
  J Biol Chem, 278, 18419-18425.  
12936985 M.A.Toleman, K.Rolston, R.N.Jones, and T.R.Walsh (2003).
Molecular and biochemical characterization of OXA-45, an extended-spectrum class 2d' beta-lactamase in Pseudomonas aeruginosa.
  Antimicrob Agents Chemother, 47, 2859-2863.  
12945052 M.Oliva, O.Dideberg, and M.J.Field (2003).
Understanding the acylation mechanisms of active-site serine penicillin-recognizing proteins: a molecular dynamics simulation study.
  Proteins, 53, 88.  
12876313 S.D.Goldberg, W.Iannuccilli, T.Nguyen, J.Ju, and V.W.Cornish (2003).
Identification of residues critical for catalysis in a class C beta-lactamase by combinatorial scanning mutagenesis.
  Protein Sci, 12, 1633-1645.  
12493831 T.Sun, M.Nukaga, K.Mayama, E.H.Braswell, and J.R.Knox (2003).
Comparison of beta-lactamases of classes A and D: 1.5-A crystallographic structure of the class D OXA-1 oxacillinase.
  Protein Sci, 12, 82-91.
PDB code: 1m6k
12395425 I.Massova, and P.A.Kollman (2002).
pKa, MM, and QM studies of mechanisms of beta-lactamases and penicillin-binding proteins: acylation step.
  J Comput Chem, 23, 1559-1576.  
11724923 D.Golemi, L.Maveyraud, S.Vakulenko, J.P.Samama, and S.Mobashery (2001).
Critical involvement of a carbamylated lysine in catalytic function of class D beta-lactamases.
  Proc Natl Acad Sci U S A, 98, 14280-14285.
PDB codes: 1k54 1k55 1k56 1k57
11709332 N.Franceschini, L.Boschi, S.Pollini, R.Herman, M.Perilli, M.Galleni, J.M.Frère, G.Amicosante, and G.M.Rossolini (2001).
Characterization of OXA-29 from Legionella (Fluoribacter) gormanii: molecular class D beta-lactamase with unusual properties.
  Antimicrob Agents Chemother, 45, 3509-3516.  
11717515 T.Sun, M.Nukaga, K.Mayama, G.V.Crichlow, A.P.Kuzin, and J.R.Knox (2001).
Crystallization and preliminary X-ray study of OXA-1, a class D beta-lactamase.
  Acta Crystallogr D Biol Crystallogr, 57, 1912-1914.  
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.