6ZIO

CRYSTAL STRUCTURE OF NRAS (C118S) IN COMPLEX WITH GDP

Summary for 6ZIO

• Entry DOI: 10.2210/pdb6zio/pdb
• Descriptor: GTPase NRas, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: gtpase, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 40183.75

Authors

Kessler, D.,Fischer, G.,Boettcher, J. (deposition date: 2020-06-26, release date: 2020-08-19, Last modification date: 2024-01-31)

Primary citation

Kessler, D.,Bergner, A.,Bottcher, J.,Fischer, G.,Dobel, S.,Hinkel, M.,Mullauer, B.,Weiss-Puxbaum, A.,McConnell, D.B.
Drugging all RAS isoforms with one pocket.
Future Med Chem, 12:1911-1923, 2020

PubMed Abstract: Activating mutations in the three human RAS genes, , and , are among the most common oncogenic drivers in human cancers. Covalent KRAS inhibitors, which bind to the switch II pocket in the 'off state' of KRAS, represent the first direct KRAS drugs that entered human clinical trials. However, the remaining 85% of non-KRAS-driven cancers remain undrugged as do NRAS and HRAS and no drugs targeting the 'on state' have been discovered so far. The switch I/II pocket is a second pocket for which the nanomolar inhibitor BI-2852 has been discovered. Here, we elucidate inhibitor binding modes in KRAS, NRAS and HRAS on and off and discuss future strategies to drug all RAS isoforms with this one pocket.

PubMed: 32779487
DOI: 10.4155/fmc-2020-0221

Experimental method

X-RAY DIFFRACTION (1.55 Å)