In:
Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 9 ( 2022-4-8)
Abstract:
Cellular sulfation pathways rely on the activated sulfate 3′-phosphoadenosine-5′-phosphosulfate (PAPS). In humans, PAPS is exclusively provided by the two PAPS synthases PAPSS1 and PAPSS2. Mutations found in the PAPSS2 gene result in severe disease states such as bone dysplasia, androgen excess and polycystic ovary syndrome. The APS kinase domain of PAPSS2 catalyzes the rate-limiting step in PAPS biosynthesis. In this study, we show that clinically described disease mutations located in the naturally fragile APS kinase domain are associated either with its destabilization and aggregation or its deactivation. Our findings provide novel insights into possible molecular mechanisms that could give rise to disease phenotypes associated with sulfation pathway genes.
Type of Medium:
Online Resource
ISSN:
2296-889X
DOI:
10.3389/fmolb.2022.860387
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2814330-9
