7N1M

Crystal Structure of the Class D Beta-lactamase OXA-935 from Pseudomonas aeruginosa, Orthorhombic Crystal Form

PDB DOI: https://doi.org/10.2210/pdb7N1M/pdb

Classification: HYDROLASE
Organism(s): Pseudomonas aeruginosa
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2021-05-27 Released: 2022-07-06
Deposition Author(s): Minasov, G., Shuvalova, L., Rosas-Lemus, M., Brunzelle, J.B., Satchell, K.J.F., Center for Structural Genomics of Infectious Diseases (CSGID)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.96 ?
R-Value Free: 0.231
R-Value Work: 0.187
R-Value Observed: 0.189

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Functional and Structural Characterization of OXA-935, a Novel OXA-10-Family beta-Lactamase from Pseudomonas aeruginosa.

Pincus, N.B., Rosas-Lemus, M., Gatesy, S.W.M., Bertucci, H.K., Brunzelle, J.S., Minasov, G., Shuvalova, L.A., Lebrun-Corbin, M., Satchell, K.J.F., Ozer, E.A., Hauser, A.R., Bachta, K.E.R.

(2022) Antimicrob Agents Chemother 66: e0098522-e0098522

PubMed: 36129295 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1128/aac.00985-22
Primary Citation of Related Structures:
7L5R, 7L5V, 7N1M

PubMed Abstract:
Resistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic β-lactamase AmpC. However, OXA-10-family β-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA β-lactamases have a propensity for mutation that leads to extended spectrum cephalosporinase and carbapenemase activity. In this study, we identified isolates from a subclade of the multidrug-resistant (MDR) high risk P. aeruginosa clonal complex CC446 with a resistance to ceftazidime. A genomic analysis revealed that these isolates harbored a plasmid containing a novel allele of bla _OXA-10, named bla _OXA-935, which was predicted to produce an OXA-10 variant with two amino acid substitutions: an aspartic acid instead of a glycine at position 157 and a serine instead of a phenylalanine at position 153. The G157D mutation, present in OXA-14, is associated with the resistance of P. aeruginosa to ceftazidime. Compared to OXA-14, OXA-935 showed increased catalytic efficiency for ceftazidime. The deletion of bla _OXA-935 restored the sensitivity to ceftazidime, and susceptibility profiling of P. aeruginosa laboratory strains expressing bla _OXA-935 revealed that OXA-935 conferred ceftazidime resistance. To better understand the impacts of the variant amino acids, we determined the crystal structures of OXA-14 and OXA-935. Compared to OXA-14, the F153S mutation in OXA-935 conferred increased flexibility in the omega (Ω) loop. Amino acid changes that confer extended spectrum cephalosporinase activity to OXA-10-family β-lactamases are concerning, given the rising reliance on novel β-lactam/β-lactamase inhibitor combinations, such as ceftolozane-tazobactam and ceftazidime-avibactam, to treat MDR P. aeruginosa infections.

Organizational Affiliation

Department of Microbiology-Immunology, Northwestern Universitygrid.16753.36, Feinberg School of Medicine, Chicago, Illinois, USA.

Macromolecule Content

Total Structure Weight: 57.56 kDa
Atom Count: 4,083
Modelled Residue Count: 477
Deposited Residue Count: 496
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-lactamase OXA-935	A, B	248	Pseudomonas aeruginosa	Mutation(s): 0 Gene Names: blaOXA-935 EC: 3.5.2.6
UniProt
Find proteins for Q06778 (Pseudomonas aeruginosa) Explore Q06778 Go to UniProtKB: Q06778
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q06778
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain N [auth A] SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] MOL2 format, chain F [auth A] MOL2 format, chain N [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] mmCIF format, chain F [auth A] mmCIF format, chain N [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B] mmCIF format, chain V [auth B] mmCIF format, chain W [auth B] mmCIF format, chain X [auth B]	C [auth A] D [auth A] E [auth A] F [auth A] G [auth A] C [auth A], D [auth A], E [auth A], F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth B], P [auth B], Q [auth B], R [auth B], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B]