Published November 27, 2020
| Version 2
Dataset
Open
Dehydrogenase E1 and transketolase domain-containing protein 1 (DHTKD1); A Target Enabling Package
Creators
- 1. Structural Genomics Consortium
- 2. Department of Biochemistry, University of Utah School of Medicine, USA
- 3. Division of Child Neurology and Metabolic Medicine, Centre for Pediatrics and Adolescent Medicine, Clinic I, University Hospital Heidelberg, Germany
Description
Inherited mutations of the GCDH gene for glutaryl-CoA dehydrogenase, catalysing the sixth enzymatic step in lysine catabolism, lead to the rare neurometabolic disorder Glutaric Aciduria type 1 (GA1). There is a rationale that inhibition of the fifth lysine catabolising step, catalysed by the DHTKD1 enzyme, could provide therapeutic benefit for GA1 by means of substrate reduction. This TEP provides early tools to develop DHTKD1 inhibitors, including recombinant protein, structure, biophysical (activity and stability) assays and fragment hits of human DHTKD1. This work also reports the interaction of DHTKD1 with its functional partner DLST as a binary complex, and an EM reconstruction of the DLST catalytic core.
Notes
This document represents version 2 of the TEP datasheet and includes all updates on the project as of November 2020. For more information about TEPs and the TEP Programme, please visit https://thesgc.org/tep.
Files
DHTKD1 TEP_v2.pdf
Files
(2.8 MB)
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Additional details
Related works
- Is part of
- https://www.thesgc.org/tep (URL)
Funding
- Wellcome Trust
- A UK Hub to Catalyse Open Target Discovery. 106169