6ZL5

CRYSTAL STRUCTURE OF KRAS-G12D(C118S) IN COMPLEX WITH BI-2852 AND GDP

Summary for 6ZL5

Entry DOI	10.2210/pdb6zl5/pdb
Descriptor	GTPase KRas, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
Functional Keywords	gtpase, hydrolase
Biological source	Homo sapiens (Human)
Total number of polymer chains	1
Total formula weight	20450.94
Authors	Kessler, D.,Fischer, G.,Boettcher, J. (deposition date: 2020-06-30, 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 Cited by 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 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.645 Å)

Structure validation