Novel druggable space in human KRAS G13D discovered using structural bioinformatics and a P-loop targeting monoclonal antibody.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
11
03
2024
accepted:
13
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
KRAS belongs to a family of small GTPases that act as binary switches upstream of several signalling cascades, controlling proliferation and survival of cells. Mutations in KRAS drive oncogenesis, especially in pancreatic, lung, and colorectal cancers (CRC). Although historic attempts at targeting mutant KRAS with small molecule inhibitors have proven challenging, there are recent successes with the G12C, and G12D mutations. However, clinically important RAS mutations such as G12V, G13D, Q61L, and A146T, remain elusive drug targets, and insights to their structural landscape is of critical importance to develop novel, and effective therapeutic concepts. We present a fully open, P-loop exposing conformer of KRAS G13D by X-ray crystallography at 1.4-2.4 Å resolution in Mg
Identifiants
pubmed: 39179604
doi: 10.1038/s41598-024-70217-9
pii: 10.1038/s41598-024-70217-9
doi:
Substances chimiques
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
KRAS protein, human
0
Antibodies, Monoclonal
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19656Informations de copyright
© 2024. The Author(s).
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