8PU5 | pdb_00008pu5

Crystal structure of the Acyl-CoA dehydrogenase FadE1(PA0506) E441A from Pseudomonas aeruginosa complexed with C16CoA

PDB DOI: https://doi.org/10.2210/pdb8PU5/pdb

Classification: OXIDOREDUCTASE
Organism(s): Pseudomonas aeruginosa
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2023-07-16 Released: 2025-02-12
Deposition Author(s): Wang, M., Brear, P., Welch, M.
Funding Organization(s): Cystic Fibrosis Trust

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.44 Å
R-Value Free:
0.214 (Depositor), 0.218 (DCC)
R-Value Work:
0.185 (Depositor), 0.194 (DCC)
R-Value Observed:
0.186 (Depositor)

Starting Models: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Pseudomonas aeruginosa acyl-CoA dehydrogenases and structure-guided inversion of their substrate specificity.

Wang, M., Medarametla, P., Kronenberger, T., Deingruber, T., Brear, P., Figueroa, W., Ho, P.M., Krueger, T., Pearce, J.C., Poso, A., Wakefield, J.G., Spring, D.R., Welch, M.

(2025) Nat Commun 16: 2334-2334

PubMed: 40057486 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-025-57532-z
Primary Citation of Related Structures:
8PNG, 8PNS, 8PU5, 8R1E

PubMed Abstract:
Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids. FadE1 displays a strong preference for long-chain acyl-CoAs, whereas FadE2 exclusively utilizes medium-chain acyl-CoAs. Structural analysis of the enzymes enables us to identify residues comprising the substrate selectivity filter in each. Engineering these residues enables us to invert the substrate specificity of each enzyme. Mutants in fadE1 displayed impaired virulence in an infection model, and decreased growth on long chain fatty acids. The unique features of the substrate binding pocket enable us to identify an inhibitor that is differentially active against FadE1 and FadE2.

Organizational Affiliation

Department of Biochemistry, Tennis Court Road, Cambridge, UK.

Macromolecule Content

Total Structure Weight: 67.22 kDa
Atom Count: 5,125
Modeled Residue Count: 599
Deposited Residue Count: 603
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Probable acyl-CoA dehydrogenase	A [auth B]	603	Pseudomonas aeruginosa	Mutation(s): 1 Gene Names: PA0506 EC: 1.3.99.41
UniProt
Find proteins for Q9I612 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)) Explore Q9I612 Go to UniProtKB: Q9I612
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9I612
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PKZ (Subject of Investigation/LOI) Query on PKZ Download Ideal Coordinates CCD File SDF format, chain B MOL2 format, chain B mmCIF format, chain B	B	Palmitoyl-CoA C₃₇ H₆₆ N₇ O₁₇ P₃ S MNBKLUUYKPBKDU-BBECNAHFSA-N		Interactions Focus chain B Interactions & Density Focus chain B
PGE Query on PGE Download Ideal Coordinates CCD File SDF format, chain E [auth B] MOL2 format, chain E [auth B] mmCIF format, chain E [auth B]	E [auth B]	TRIETHYLENE GLYCOL C₆ H₁₄ O₄ ZIBGPFATKBEMQZ-UHFFFAOYSA-N		Interactions Focus chain E [auth B] Interactions & Density Focus chain E [auth B]
TRS Query on TRS Download Ideal Coordinates CCD File SDF format, chain J [auth B] MOL2 format, chain J [auth B] mmCIF format, chain J [auth B]	J [auth B]	2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL C₄ H₁₂ N O₃ LENZDBCJOHFCAS-UHFFFAOYSA-O		Interactions Focus chain J [auth B] Interactions & Density Focus chain J [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain C [auth B] SDF format, chain D [auth B] SDF format, chain F [auth B] SDF format, chain G [auth B] MOL2 format, chain C [auth B] MOL2 format, chain D [auth B] MOL2 format, chain F [auth B] MOL2 format, chain G [auth B] mmCIF format, chain C [auth B] mmCIF format, chain D [auth B] mmCIF format, chain F [auth B] mmCIF format, chain G [auth B]	C [auth B], D [auth B], F [auth B], G [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain C [auth B] Focus chain D [auth B] Focus chain F [auth B] Focus chain G [auth B] Interactions & Density Focus chain C [auth B] Focus chain D [auth B] Focus chain F [auth B] Focus chain G [auth B]
NO3 Query on NO3 Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B]	H [auth B], I [auth B]	NITRATE ION N O₃ NHNBFGGVMKEFGY-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain H [auth B] Focus chain I [auth B]