› 9axx

X-ray diffraction
2.07Å resolution

Crystal structure of BRAF/MEK1 complex with NST-628 and an active RAF dimer

Released:
DOI: 10.2210/pdb9axx/pdb
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PDB entry 9axx coloured by chain, front view.
PDB entry 9axx coloured by chain, side view.
PDB entry 9axx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The pan-RAF-MEK non degrading molecular glue NST-628 is a potent and brain penetrant inhibitor of the RAS-MAPK pathway with activity across diverse RAS- and RAF-driven cancers.
Ryan MB, Quade B, Schenk N, Fang Z, Zingg M, Cohen SE, Swalm BM, Li C, Ozen A, Ye C, Ritorto MS, Huang X, Dar AC, Han Y, Hoeflich KP, Hale M, Hagel M
OpenAccess logo Cancer Discov (2024)
PMID: 38588399

Function and Biology Details

Reactions catalysed: 
ATP + L-seryl/L-threonyl/L-tyrosyl-[protein] = ADP + O-phospho-L-seryl/O-phospho-L-threonyl/O-phospho-L-tyrosyl-[protein]
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-147202 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Dual specificity mitogen-activated protein kinase kinase 1 Chains: A, C
Molecule details ›
Chains: A, C
Length: 310 amino acids
Theoretical weight: 34.54 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q02750 (Residues: 37-263, 308-383; Coverage: 77%)
Gene names: MAP2K1, MEK1, PRKMK1
Sequence domains: Protein kinase domain
Serine/threonine-protein kinase B-raf Chains: B, D
Molecule details ›
Chains: B, D
Length: 280 amino acids
Theoretical weight: 31.83 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P15056 (Residues: 445-723; Coverage: 36%)
Gene names: BRAF, BRAF1, RAFB1
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

5 bound ligands:
Ligand A1AHE 2 x A1AHE
Ligand ANP 3 x ANP
Ligand MG 2 x MG
Ligand EDO 11 x EDO
Ligand TRS 1 x TRS
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: DIAMOND BEAMLINE I03
Spacegroup: P21
Unit cell:
a: 72.213Å b: 82.408Å c: 121.552Å
α: 90° β: 105.65° γ: 90°
R-values:
R R work R free
0.215 0.213 0.248
Expression system: Homo sapiens

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