4TX6

AfChiA1 in complex with compound 1

PDB DOI: https://doi.org/10.2210/pdb4TX6/pdb

Classification: HYDROLASE
Organism(s): Aspergillus fumigatus A1163
Expression System: Komagataella pastoris
Mutation(s): No

Deposited: 2014-07-02 Released: 2014-08-06
Deposition Author(s): van Aalten, D.M.F.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.184
R-Value Work: 0.154
R-Value Observed: 0.156

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Screening-based discovery of Aspergillus fumigatus plant-type chitinase inhibitors

Lockhart, D.E., Schuettelkopf, A.W., Blair, D.E., van Aalten, D.M.F.

(2014) FEBS Lett 588: 3282

PubMed: 25063338 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1016/j.febslet.2014.07.015
Primary Citation of Related Structures:
4TX6, 4TXE

PubMed Abstract:
A limited therapeutic arsenal against increasing clinical disease due to Aspergillus spp. necessitates urgent characterisation of new antifungal targets. Here we describe the discovery of novel, low micromolar chemical inhibitors of Aspergillus fumigatus family 18 plant-type chitinase A1 (AfChiA1) by high-throughput screening (HTS). Analysis of the binding mode by X-ray crystallography confirmed competitive inhibition and kinetic studies revealed two compounds with selectivity towards fungal plant-type chitinases. These inhibitors provide new chemical tools to probe the effects of chitinase inhibition on A. fumigatus growth and virulence, presenting attractive starting points for the development of further potent drug-like molecules.

Organizational Affiliation

Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.

Macromolecule Content

Total Structure Weight: 70.04 kDa
Atom Count: 5,714
Modelled Residue Count: 619
Deposited Residue Count: 620
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Class III chitinase ChiA1	A, B	310	Aspergillus fumigatus A1163	Mutation(s): 0 Gene Names: AFUB_052270
UniProt
Find proteins for B0Y2Y2 (Aspergillus fumigatus (strain CBS 144.89 / FGSC A1163 / CEA10)) Explore B0Y2Y2 Go to UniProtKB: B0Y2Y2
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	B0Y2Y2
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
38B Query on 38B Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain L [auth B] MOL2 format, chain C [auth A] MOL2 format, chain L [auth B]	C [auth A], L [auth B]	3-(2-methoxyphenyl)-6-methyl[1,2]oxazolo[5,4-d]pyrimidin-4(5H)-one C₁₃ H₁₁ N₃ O₃ XCLPDGVIHJQQOR-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain L [auth B] Interactions & Density Focus chain C [auth A] Focus chain L [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [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 M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [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 M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B]	D [auth A] E [auth A] F [auth A] G [auth A] H [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], M [auth B], N [auth B], O [auth B], P [auth B], Q [auth B], R [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions 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 M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Interactions & Density 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 M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B]