Human peroxisomal coenzyme A diphosphatase (NUDT7): a target enabling package (TEP)

Velupillai, Srikannathasan, Sáez, Laura Díaz, Krojer, Tobias, Bennett, James, Ruda, Gian Filippo, Szommer, Tamas, Straub, Verena, Nunez Alonso, Graciela, Siejka, Paulina, Bradley, Anthony, Talon, Romain, Fairhead, Michael, Elkins, Jon, London, Nir, Spencer, John, von Delft, Frank, Fedorov, Oleg, Brennan, Paul and Huber, Kilian (2018) Human peroxisomal coenzyme A diphosphatase (NUDT7): a target enabling package (TEP). Zenodo. pp. 1-15.

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB)

Abstract

In an effort to characterise the human NUDIX family SGC Oxford has expressed recombinant human NUDT7 as part of the SGC chemical probe programme and solved the first crystal structure of this enzyme. This enabled a crystallographic fragment screen which in conjunction with a separate covalent fragment approach yielded a first-in-class small molecule inhibitor of NUDT7 with activity in the single-digit micromolar range in a catalytic assay. This compound paves the way for chemical probe development and further functional exploration of NUDT7 in physiological and disease contexts.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science
Q Science > QD Chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Q Science > QD Chemistry > QD0901 Crystallography
Depositing User: John Spencer
Date Deposited: 25 Oct 2019 11:45
Last Modified: 30 Sep 2020 09:45
URI: http://sro.sussex.ac.uk/id/eprint/87429

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
A Precompetitive Modular Peptidomimetic Toolkit for Targeting PPIs iCASE AZG1623ASTRAZENECAUnset