8B78: KRasG12C ligand complex

KRasG12C ligand complex. Determined by X-ray diffraction at 1.11 Å resolution. Released 12 Jul 2023.

Method: X-ray diffraction
Resolution: 1.11 Å
Organism: Homo sapiens
Chains: 1
Atoms: 1,524
Mol. weight: 20.11 kDa
Ligands: PUO, GDP, MG
Released: 12 Jul 2023

Explore 8B78 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8B78 contains 5 α-helices and 6 β-strands across 1 chain. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 5 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	2-9	8	1
α-helix	16-25	10
β-strand	38-46	9	1
β-strand	49-57	9	1
α-helix	66-74	9
β-strand	77-83	7	1
α-helix	87-104	18
β-strand	111-116	6	1
α-helix	127-137	11
β-strand	141-143	3	1
α-helix	152-166	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
GTPase KRas	A	protein	168	Homo sapiens	P01116 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8B78_1 GTPase KRas (chains A)
GMTEYKLVVVGACGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETSLLDILDTA
GQEEYSAMRDQYMRTGEGFLLVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKSD
LPSRTVDTKQAQDLARSYGIPFIETSAKTRQRVDDAFYTLVREIRKHK

Ligands and cofactors

ID	Name	Formula	Copies
PUO	1-[(4~{a}~{R})-8-(2-chloranyl-6-oxidanyl-phenyl)-7-fluoranyl-9-prop-1-ynyl-1,2,…	C24 H24 Cl F N2 O3	1
GDP	Guanosine-5'-diphosphate	C10 H15 N5 O11 P2	1
MG	Magnesium ion	Mg	1

Primary citation

Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRAS G12C with Demonstrable CNS Penetration. Kettle, J.G., Bagal, S.K., Barratt, D. et al. J Med Chem (2023) 66:9147-9160. DOI 10.1021/acs.jmedchem.3c00746 · PubMed

Other PDB entries of the same protein (UniProt P01116 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9IAY 0.95 Å, Structure of 10 in complex with GDP-KRAS
9IAW 1.0 Å, Structure of 5 in complex with GDP-KRAS
12XE 1.01 Å, Crystal structure of KRAS(Q61K) bound to GppNHp and ligand
8ONV 1.01 Å, KRAS-G13D in complex with BI-2493
6P0Z 1.01 Å, Crystal structure of N-acetylated KRAS (2-169) bound to GDP and Mg
9IB5 1.01 Å, Structure of 18 (BI-2493) in complex with GDP-KRAS
8AZZ 1.02 Å, KRAS-G12V in complex with BI-2865
8AZX 1.04 Å, KRAS-G12C in complex with BI-2865
8B00 1.04 Å, KRAS-G13D in complex with BI-2865
8TVK 1.04 Å, KRAS 1-169 G12C Mutant at 100k
4QL3 1.04 Å, Crystal Structure of a GDP-bound G12R Oncogenic Mutant of Human GTPase KRas
8AZV 1.05 Å, KRAS in complex with BI-2865

Browse structure collections

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