› 1rr8

X-ray diffraction
2.6Å resolution

Structural Mechanisms of Camptothecin Resistance by Mutations in Human Topoisomerase I

Released:
DOI: 10.2210/pdb1rr8/pdb
PDB 1rr8 coloured by chain and viewed from the front.
PDB 1rr8 coloured by chain and viewed from the side.
PDB 1rr8 coloured by chain and viewed from the top.
Source organism: Homo sapiens
Primary publication:
Mechanisms of camptothecin resistance by human topoisomerase I mutations.
Chrencik JE, Staker BL, Burgin AB, Pourquier P, Pommier Y, Stewart L, Redinbo MR
J Mol Biol 339 773-84 (2004)
PMID: 15165849

Function and Biology Details

Reaction catalysed: 
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:
Structure domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Entry contents:
1 distinct polypeptide molecule
2 distinct DNA molecules
Macromolecules (3 distinct):
DNA topoisomerase 1 Chain: C
Molecule details ›
Chain: C
Length: 565 amino acids
Theoretical weight: 66.79 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P11387 (Residues: 203-765; Coverage: 74%)
Gene name: TOP1
Sequence domains:
Structure domains:
5'-D(*AP*AP*AP*AP*AP*GP*AP*CP*TP*T*GP*GP*AP*AP*AP*AP*AP*TP*TP*TP*TP*T)-3' Chain: A
Molecule details ›
Chain: A
Length: 22 nucleotides
Theoretical weight: 6.81 KDa
Source organism: Homo sapiens
Expression system: Not provided
5'-D(*AP*AP*AP*AP*AP*TP*TP*TP*TP*TP*CP*CP*AP*AP*GP*TP*CP*TP*TP*TP*TP*T)-3' Chain: B
Molecule details ›
Chain: B
Length: 22 nucleotides
Theoretical weight: 6.69 KDa
Source organism: Homo sapiens
Expression system: Not provided

Ligands and Environments

2 bound ligands:
Ligand TTG 1 x TTG
Ligand TTC 1 x TTC
1 modified residue:
Ligand PTR 1 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: P21
Unit cell:
a: 57.59Å b: 115.585Å c: 75.01Å
α: 90° β: 96.29° γ: 90°
R-values:
R R work R free
0.242 0.242 0.294
Expression systems:
  • Spodoptera frugiperda
  • Not provided

Quick links

Citations

15 review citations

Topoisomerase 1B poisons: Over a half-century of drug leads, clinical candidates, and serendipitous discoveries.
Cinelli MA. (2019)
14 more

1 mention without citation

In-silico prediction of drug targets, biological activities, signal pathways and regulating networks of dioscin based on bioinformatics.
Yin et al. (2015)