› 7pi4

X-ray diffraction
2.24Å resolution

FAK Protac GSK215 in complex with FAK and pVHL:ElonginC:ElonginB

Released:
DOI: 10.2210/pdb7pi4/pdb
PDB entry 7pi4 coloured by chain, front view.
PDB entry 7pi4 coloured by chain, side view.
PDB entry 7pi4 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs.
Law RP, Nunes J, Chung CW, Bantscheff M, Buda K, Dai H, Evans JP, Flinders A, Klimaszewska D, Lewis AJ, Muelbaier M, Scott-Stevens P, Stacey P, Tame CJ, Watt GF, Zinn N, Queisser MA, Harling JD, Benowitz AB
Angew Chem Int Ed Engl 60 23327-23334 (2021)
PMID: 34416073

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
PDBe Complex ID:
PDB-CPX-154082 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (4 distinct):
von Hippel-Lindau disease tumor suppressor Chain: AAA
Molecule details ›
Chain: AAA
Length: 155 amino acids
Theoretical weight: 18.01 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P40337 (Residues: 59-213; Coverage: 73%)
Gene name: VHL
Sequence domains:
Elongin-B Chain: BBB
Molecule details ›
Chain: BBB
Length: 105 amino acids
Theoretical weight: 11.85 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q15370 (Residues: 1-105; Coverage: 89%)
Gene names: ELOB, TCEB2
Sequence domains: Ubiquitin family
Isoform 2 of Elongin-C Chain: CCC
Molecule details ›
Chain: CCC
Length: 96 amino acids
Theoretical weight: 10.84 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q15369-2 (Residues: 1-96; Coverage: 100%)
Gene names: ELOC, TCEB1
Focal adhesion kinase 1 Chain: DDD
Molecule details ›
Chain: DDD
Length: 273 amino acids
Theoretical weight: 31.38 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q05397 (Residues: 415-687; Coverage: 26%)
Gene names: FAK, FAK1, PTK2
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

4 bound ligands:
Ligand 7QB 1 x 7QB
Ligand PEG 4 x PEG
Ligand EDO 14 x EDO
Ligand CA 1 x CA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U1
Spacegroup: P212121
Unit cell:
a: 59.55Å b: 77.26Å c: 175.18Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.198 0.195 0.251
Expression systems:
  • Escherichia coli BL21(DE3)
  • Spodoptera frugiperda

Quick links

Citations

6 review citations

PROTACs: past, present and future.
Li et al. (2022)
5 more

5 mentions without citation

Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders.
Diehl et al. (2022)
4 more