PDBsum entry 1e4d

Beta-lactamase

PDB id: 1e4d

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:

1.80Å R-factor: 0.198 R-free: 0.243

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

Protein chains

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

Seq: 266 a.a.

Struc: 243 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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: 10.1016/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.