4WZ5

Crystal structure of P. aeruginosa OXA10

PDB DOI: https://doi.org/10.2210/pdb4WZ5/pdb

Classification: hydrolase/hydrolase inhibitor
Organism(s): Pseudomonas aeruginosa
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2014-11-18 Released: 2015-08-05
Deposition Author(s): Ferguson, A.D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.60 Å
R-Value Free: 0.208
R-Value Work: 0.190
R-Value Observed: 0.191

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

4,5-Disubstituted 6-Aryloxy-1,3-dihydrobenzo[c][1,2]oxaboroles Are Broad-Spectrum Serine beta-Lactamase Inhibitors.

McKinney, D.C., Zhou, F., Eyermann, C.J., Ferguson, A.D., Prince, D.B., Breen, J., Giacobbe, R.A., Lahiri, S., Verheijen, J.C.

(2015) ACS Infect Dis 1: 310-316

PubMed: 27622821 Search on PubMed
DOI: https://doi.org/10.1021/acsinfecdis.5b00031
Primary Citation of Related Structures:
4WYY, 4WZ4, 4WZ5

PubMed Abstract:
Bacterially expressed β-lactamases are rapidly eroding the clinical utility of the important β-lactam class of antibacterials, significantly impairing our ability to fight serious bacterial infections. This paper describes a study of oxaborole-derived β-lactamase inhibitors in which crystal structures and computational modeling aided in the rational design of analogues with improved spectrum of activity against class A, C, and D enzymes. Crystal structures of two of these inhibitors covalently bound to two different serine β-lactamases, class C Pseudomonas aeruginosa AmpC and class D OXA-10, are described herein. Improved physicochemical properties as well as increased activity against an array of β-lactamases resulted in substantial restoration of susceptibility to ceftazidime in Escherichia coli and Klebsiella pneumoniae.

Organizational Affiliation

Infection Innovative Medicines, AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham Massachusetts 02451, United States.

Macromolecule Content

Total Structure Weight: 112.94 kDa
Atom Count: 8,380
Modelled Residue Count: 980
Deposited Residue Count: 992
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-lactamase OXA-10	A, B	248	Pseudomonas aeruginosa	Mutation(s): 0 Gene Names: bla, oxa10, pse2 EC: 3.5.2.6
UniProt
Find proteins for P14489 (Pseudomonas aeruginosa) Explore P14489 Go to UniProtKB: P14489
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P14489
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-lactamase OXA-10	C, D	248	Pseudomonas aeruginosa	Mutation(s): 0 Gene Names: bla, oxa10, pse2 EC: 3.5.2.6
UniProt
Find proteins for P14489 (Pseudomonas aeruginosa) Explore P14489 Go to UniProtKB: P14489
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P14489
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
3VU Query on 3VU Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain K [auth B] MOL2 format, chain G [auth A] MOL2 format, chain K [auth B]	G [auth A], K [auth B]	{(3R)-6-[(3-amino-1,2,4-thiadiazol-5-yl)oxy]-1-hydroxy-4,5-dimethyl-1,3-dihydro-2,1-benzoxaborol-3-yl}acetic acid C₁₃ H₁₄ B N₃ O₅ S CXFHZAGALDYYDH-SECBINFHSA-N		Interactions Focus chain G [auth A] Focus chain K [auth B] Interactions & Density Focus chain G [auth A] Focus chain K [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain L [auth C] SDF format, chain M [auth C] SDF format, chain N [auth C] SDF format, chain O [auth C] SDF format, chain Q [auth D] SDF format, chain R [auth D] SDF format, chain S [auth D] SDF format, chain T [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain L [auth C] MOL2 format, chain M [auth C] MOL2 format, chain N [auth C] MOL2 format, chain O [auth C] MOL2 format, chain Q [auth D] MOL2 format, chain R [auth D] MOL2 format, chain S [auth D] MOL2 format, chain T [auth D]	E [auth A] F [auth A] H [auth B] I [auth B] J [auth B] E [auth A], F [auth A], H [auth B], I [auth B], J [auth B], L [auth C], M [auth C], N [auth C], O [auth C], Q [auth D], R [auth D], S [auth D], T [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Focus chain L [auth C] Focus chain M [auth C] Focus chain N [auth C] Focus chain O [auth C] Focus chain Q [auth D] Focus chain R [auth D] Focus chain S [auth D] Focus chain T [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Focus chain L [auth C] Focus chain M [auth C] Focus chain N [auth C] Focus chain O [auth C] Focus chain Q [auth D] Focus chain R [auth D] Focus chain S [auth D] Focus chain T [auth D]
CO2 Query on CO2 Download Ideal Coordinates CCD File SDF format, chain P [auth C] SDF format, chain U [auth D] MOL2 format, chain P [auth C] MOL2 format, chain U [auth D]	P [auth C], U [auth D]	CARBON DIOXIDE C O₂ CURLTUGMZLYLDI-UHFFFAOYSA-N		Interactions Focus chain P [auth C] Focus chain U [auth D] Interactions & Density Focus chain P [auth C] Focus chain U [auth D]