PDBsum entry 1m6k

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
250 a.a. *
MPD ×10
Waters ×559
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of the oxa-1 class d beta-lactamase
Structure: Beta-lactamase oxa-1. Chain: a, b. Synonym: penicillinase, oxacillinase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: oxa1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
1.50Å     R-factor:   0.182     R-free:   0.203
Authors: T.Sun,M.Nukaga,K.Mayama,E.H.Braswell,J.R.Knox
Key ref:
T.Sun et al. (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. PubMed id: 12493831 DOI: 10.1110/ps.0224303
16-Jul-02     Release date:   14-Jan-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P13661  (BLO1_ECOLX) -  Beta-lactamase OXA-1
276 a.a.
250 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.  - Beta-lactamase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

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: 10.1110/ps.0224303 Protein Sci 12:82-91 (2003)
PubMed id: 12493831  
Comparison of beta-lactamases of classes A and D: 1.5-A crystallographic structure of the class D OXA-1 oxacillinase.
T.Sun, M.Nukaga, K.Mayama, E.H.Braswell, J.R.Knox.
The crystallographic structure of the Escherichia coli OXA-1 beta-lactamase has been established at 1.5-A resolution and refined to R = 0.18. The 28.2-kD oxacillinase is a class D serine beta-lactamase that is especially active against the penicillin-type beta-lactams oxacillin and cloxacillin. In contrast to the structures of OXA-2, OXA-10, and OXA-13 belonging to other subclasses, the OXA-1 molecule is monomeric rather than dimeric and represents the subclass characterized by an enlarged Omega loop near the beta-lactam binding site. The 6-residue hydrophilic insertion in this loop cannot interact directly with substrates and, instead, projects into solvent. In this structure at pH 7.5, carboxylation of the conserved Lys 70 in the catalytic site is observed. One oxygen atom of the carboxylate group is hydrogen bonded to Ser 120 and Trp 160. The other oxygen atom is more exposed and hydrogen bonded to the Ogamma of the reactive Ser 67. In the overlay of the class D and class A binding sites, the carboxylate group is displaced ca. 2.6 A from the carboxylate group of Glu 166 of class A enzymes. However, each group is equidistant from the site of the water molecule expected to function in hydrolysis, and which could be activated by the carboxylate group of Lys 70. In this ligand-free OXA-1 structure, no water molecule is seen in this site, so the water molecule must enter after formation of the acyl-Ser 67 intermediate.
  Selected figure(s)  
Figure 2.
Figure 2. 2Fo-Fc electron density map showing groups in the catalytic site near the carboxylated Lys 70 side chain. Contoured at 1.2 . Hydrogen bonds are indicated by broken lines. The map was drawn by CHAIN (Sack and Quiocho 1997).
Figure 8.
Figure 8. Carboxylation of Lys 70, and a -lactam hydrolysis mechanism for class D -lactamases, adapted from Maveyraud et al. (2002). Proton transfer to the thiazole leaving group via Ser 115 could proceed by either of two paths.
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 82-91) copyright 2003.  
  Figures were 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.  
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.  
19919101 K.D.Schneider, M.E.Karpen, R.A.Bonomo, D.A.Leonard, and R.A.Powers (2009).
The 1.4 A crystal structure of the class D beta-lactamase OXA-1 complexed with doripenem.
  Biochemistry, 48, 11840-11847.
PDB code: 3isg
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.  
18719182 S.M.Mortimer-Jones, N.D.Phillips, T.La, R.Naresh, and D.J.Hampson (2008).
Penicillin resistance in the intestinal spirochaete Brachyspira pilosicoli associated with OXA-136 and OXA-137, two new variants of the class D beta-lactamase OXA-63.
  J Med Microbiol, 57, 1122-1128.  
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
17223624 F.Depardieu, I.Podglajen, R.Leclercq, E.Collatz, and P.Courvalin (2007).
Modes and modulations of antibiotic resistance gene expression.
  Clin Microbiol Rev, 20, 79.  
17220410 J.M.Thomson, F.Prati, C.R.Bethel, and R.A.Bonomo (2007).
Use of novel boronic acid transition state inhibitors to probe substrate affinity in SHV-type extended-spectrum beta-lactamases.
  Antimicrob Agents Chemother, 51, 1577-1579.  
16870757 C.Voha, J.D.Docquier, G.M.Rossolini, and T.Fosse (2006).
Genetic and biochemical characterization of FUS-1 (OXA-85), a narrow-spectrum class D beta-lactamase from Fusobacterium nucleatum subsp. polymorphum.
  Antimicrob Agents Chemother, 50, 2673-2679.  
17000742 K.M.Hujer, A.M.Hujer, E.A.Hulten, S.Bajaksouzian, J.M.Adams, C.J.Donskey, D.J.Ecker, C.Massire, M.W.Eshoo, R.Sampath, J.M.Thomson, P.N.Rather, D.W.Craft, J.T.Fishbain, A.J.Ewell, M.R.Jacobs, D.L.Paterson, and R.A.Bonomo (2006).
Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center.
  Antimicrob Agents Chemother, 50, 4114-4123.  
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.  
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.  
15793160 K.E.Keith, P.C.Oyston, B.Crossett, N.F.Fairweather, R.W.Titball, T.R.Walsh, and K.A.Brown (2005).
Functional characterization of OXA-57, a class D beta-lactamase from Burkholderia pseudomallei.
  Antimicrob Agents Chemother, 49, 1639-1641.  
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.  
15461559 N.H.Georgopapadakou (2004).
Beta-lactamase inhibitors: evolving compounds for evolving resistance targets.
  Expert Opin Investig Drugs, 13, 1307-1318.  
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.  
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.