› 1k4s

X-ray diffraction
3.2Å resolution

HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX

Released:
DOI: 10.2210/pdb1k4s/pdb
PDB entry 1k4s coloured by chain, front view.
PDB entry 1k4s coloured by chain, side view.
PDB entry 1k4s coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The mechanism of topoisomerase I poisoning by a camptothecin analog.
Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB, Stewart L
Proc Natl Acad Sci U S A 99 15387-92 (2002)
PMID: 12426403

Function and Biology Details

Reaction catalysed: 
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Biochemical function:
Biological process:
Cellular component:
Sequence domains:
Structure domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-114048 (preferred)
Entry contents:
1 distinct polypeptide molecule
3 distinct DNA molecules
Macromolecules (4 distinct):
DNA topoisomerase 1 Chain: A
Molecule details ›
Chain: A
Length: 592 amino acids
Theoretical weight: 70.25 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P11387 (Residues: 174-765; Coverage: 77%)
Gene name: TOP1
Sequence domains:
Structure domains:
5'-D(*AP*AP*AP*AP*AP*GP*AP*CP*(5IU)P*(5IU))-3' Chain: B
Molecule details ›
Chain: B
Length: 10 nucleotides
Theoretical weight: 3.28 KDa
Source organism: Homo sapiens
Expression system: Not provided
5'-D(*(SPT)P*GP*AP*AP*AP*AP*AP*(5IU)P*(5IU)P*(5IU)P*(5IU)P*T)-3' Chain: C
Molecule details ›
Chain: C
Length: 12 nucleotides
Theoretical weight: 4.14 KDa
Source organism: Homo sapiens
Expression system: Not provided
5'-D(*AP*AP*AP*AP*AP*TP*(IDO)UP*(IDO)UP*(IDO)UP*(IDO)UP*CP*AP*AP*AP*GP*(IDO)UP*CP*(IDO)UP*(IDO)UP*(IDO)UP*(IDO)UP*T)-3' Chain: D
Molecule details ›
Chain: D
Length: 22 nucleotides
Theoretical weight: 7.72 KDa
Source organism: Homo sapiens
Expression system: Not provided

Ligands and Environments

No bound ligands
3 modified residues:
Ligand 5IU 15 x 5IU
Ligand SPT 1 x SPT
Ligand PTR 1 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: P32
Unit cell:
a: 73.235Å b: 73.235Å c: 186.632Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.217 0.217 0.222
Expression systems:
  • Spodoptera frugiperda
  • Not provided

Quick links

Citations

68 review citations

Topoisomerase I inhibitors: camptothecins and beyond.
Pommier Y. (2006)
67 more

18 mentions without citation

Interfacial inhibitors.
Pommier et al. (2015)
17 more