Research workbench
Identification of the clinical development candidate MRTX849, a covalent KRASG12C inhibitor for the treatment of cancer
Analyse Identification of the clinical development candidate MRTX849, a covalent… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.
- PDB
- 6UT0
- Type
- protein
- Length
- 677 residues
- Chains
- 4
- Method
- x-ray diffraction
- Collection
- MolNFT v1 / PDB
- Contract
- 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
- Owner
- 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
- Molecule
- GTPase KRAS
- UniProt
- P01116
- Ligands
- GDP, M1X, MG
- Pockets
- 7 · best druggability 0.79
Structure
x-ray diffraction · 3 distinct chains · 37% helix, 25% strand (DSSP).
| Chain | Molecule | Type | Residues | Secondary structure | UniProt |
|---|---|---|---|---|---|
| A | GTPase KRAS | protein | 169 | 37% helix, 24% strand | P01116 |
| B | GTPase KRAS | protein | 168 | 37% helix, 26% strand | P01116 |
| C, D | GTPase KRAS | protein | 170 | 37% helix, 25% strand | P01116 |
Ligands and binding sites
- GDP · Guanosine-5'-diphosphate · ligand · 4 copies · chains A, B, C, D
- M1X · {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-[(2S)-2-fluoropropanoyl]piperazin-2-yl}acetonitrile · ligand · 4 copies · chains A, B, C, D
- MG · Magnesium ion · metal · 4 copies · chains A, B, C, D
Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.
Pockets
7 pockets found on a 1 Å grid, 6 with a druggability of 0.5 or more.
| Volume (ų) | Druggability | Buriedness | Lining residues | Inside | |
|---|---|---|---|---|---|
| 1 | 694 | 0.79 | 0.83 | 69 | GDP, MG, M1X |
| 2 | 357 | 0.74 | 0.85 | 48 | GDP, MG, M1X |
| 3 | 309 | 0.70 | 0.84 | 43 | GDP, MG, M1X |
| 4 | 301 | 0.69 | 0.83 | 43 | GDP, MG, M1X |
| 5 | 415 | 0.64 | 0.78 | 32 | empty |
Interfaces
5 interfaces between chains.
- B–D · 575 Ų buried · 12 hydrogen bonds · protein-protein
- A–C · 430 Ų buried · 6 hydrogen bonds · protein-protein
- A–B · 217 Ų buried · 3 hydrogen bonds · protein-protein
- C–D · 123 Ų buried · 1 hydrogen bond · protein-protein
- B–C · 62 Ų buried · 0 hydrogen bonds · protein-protein
Modifications
Observed in the structure: 4 covalent (covalent ligand).
Compared structures
- 6UT0 · Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C… · the same entry in another collection · chain A against A, TM-score 1.00
Analyse
- Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
- Every structure of UniProt P01116
- Elsewhere: RCSB PDB 6UT0 · PDBe 6UT0 · UniProt P01116
GL1X is a live explorer of the GenesisL1 blockchain. Turn on JavaScript for search, charts and interactive views.