PDBsum entry 4txe

Hydrolase

PDB id: 4txe

Contents

Protein chain

288 a.a.

Ligands

38F

Waters ×210

PDB id:

4txe

Name:

Hydrolase

Title:

Sccts1 in complex with compound 5

Structure:

Endochitinase. Chain: a. Fragment: unp residues 22-315. Synonym: soluble cell wall protein 2. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: cts1, scw2, ylr286c, l8003.13. Expressed in: komagataella pastoris. Expression_system_taxid: 4922

Resolution:

1.80Å R-factor: 0.162 R-free: 0.191

Authors:

A.W.Schuettelkopf,D.M.F.Van Aalten

Key ref:

D.E.Lockhart et al. (2014). Screening-based discovery of Aspergillus fumigatus plant-type chitinase inhibitors. Febs Lett, 588, 3282-3290. PubMed id: 25063338 DOI: 10.1016/j.febslet.2014.07.015

Date:

03-Jul-14 Release date: 06-Aug-14

Protein chain

P29029  (CHIT_YEAST) -  Endochitinase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 562 a.a.

Struc: 288 a.a.

Enzyme reactions

• Enzyme class: E.C.3.2.1.14 - chitinase.
• Reaction: Hydrolysis of the 1,4-beta-linkages of N-acetyl-D-glucosamine polymers of chitin.

DOI no: 10.1016/j.febslet.2014.07.015

Febs Lett 588:3282-3290 (2014)

PubMed id: 25063338

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

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

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.