PDBsum entry 1fof

Hydrolase

PDB id: 1fof

Contents

Protein chains

246 a.a. *

Ligands

SO4 ×2

Metals

_CO ×2

Waters ×467

* Residue conservation analysis

PDB id:

1fof

Name:

Hydrolase

Title:

Crystal structure of the class d beta-lactamase oxa-10

Structure:

Beta lactamase oxa-10. Chain: a, b. Synonym: oxa-10. Engineered: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.177 R-free: 0.208

Authors:

M.Paetzel,F.Danel,L.De Castro,S.C.Mosimann,M.G.P.Page,N.C.J.Strynadka

Key ref:

M.Paetzel et al. (2000). Crystal structure of the class D beta-lactamase OXA-10. Nat Struct Biol, 7, 918-925. PubMed id: 11017203 DOI: 10.1038/79688

Date:

28-Aug-00 Release date: 09-Oct-00

Protein chains

P14489  (BLO10_PSEAI) -  Beta-lactamase OXA-10 from Pseudomonas aeruginosa

Seq: 266 a.a.

Struc: 246 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.2.6 - beta-lactamase.
• Pathway: Penicillin Biosynthesis and Metabolism
• Reaction: a beta-lactam + H2O = a substituted beta-amino acid
• Cofactor: Zn(2+)

DOI no: 10.1038/79688

Nat Struct Biol 7:918-925 (2000)

PubMed id: 11017203

Crystal structure of the class D beta-lactamase OXA-10.

M.Paetzel, F.Danel, L.de Castro, S.C.Mosimann, M.G.Page, N.C.Strynadka.

ABSTRACT

We report the crystal structure of a class D beta-lactamase, the broad spectrum enzyme OXA-10 from Pseudomonas aeruginosa at 2.0 A resolution. There are significant differences between the overall fold observed in this structure and those of the evolutionarily related class A and class C beta-lactamases. Furthermore, the structure suggests the unique, cation mediated formation of a homodimer. Kinetic and hydrodynamic data shows that the dimer is a relevant species in solution and is the more active form of the enzyme. Comparison of the molecular details of the active sites of the class A and class C enzymes with the OXA-10 structure reveals that there is no counterpart in OXA-10 to the residues proposed to act as general bases in either of these enzymes (Glu 166 and Tyr 150, respectively). Our structures of the native and chloride inhibited forms of OXA-10 suggest that the class D enzymes have evolved a distinct catalytic mechanism for beta-lactam hydrolysis. Clinical variants of OXA-10 are also discussed in light of the structure.

Selected figure(s)

Figure 3.
Figure 3. Superpositions of the overall fold of class D OXA-10 with related enzymes. a, Stereo view of the superposition of OXA-10 (gray ribbon43) with a representative class A -lactamase (E. coli TEM-1^10, 11, red ribbon, PDB accession code 1FQG). b, Stereo view of the superposition with a representative class C -lactamase (C. freundii12, green ribbon, PDB accession code 1FR6). c, Stereo view of the superposition with the transpeptidase domain of PBP2x (S. pneumoniae^6, blue ribbon, PDB accession code 1QME).

Figure 4.
Figure 4. The OXA-10 homodimer. a, Stereo view of a ribbon representation43 of the observed OXA-10 homodimer. One monomer is in green and gold, the other in blue and red. The two cobalt atoms that lie at the dimer interface are shown in dark blue. The active site residues Ser 67 and Lys 70 are shown in ball and stick representation. It should be noted that the active site of each monomer lies on the same face of the dimer and are 40 Å apart. b, Stereo view of the coordination of the cobalt atoms (blue) by the coordinating ligands Glu 227 and His 203 within one monomer and Glu 190 within the second monomer. Two ordered waters (small spheres) complete the approximate octahedral coordination of each cobalt. The refined temperature factor of each cobalt atom is 19.5 Å2.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 918-925) copyright 2000.

Figures were selected by an automated process.