1UK0

Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase with a novel inhibitor

PDB DOI: https://doi.org/10.2210/pdb1UK0/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2003-08-13 Released: 2004-01-27
Deposition Author(s): Kinoshita, T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.246
R-Value Work: 0.219

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Inhibitor-induced structural change of the active site of human poly(ADP-ribose) polymerase.

Kinoshita, T., Nakanishi, I., Warizaya, M., Iwashita, A., Kido, Y., Hattori, K., Fujii, T.

(2004) FEBS Lett 556: 43-46

PubMed: 14706823 Search on PubMed
DOI: https://doi.org/10.1016/s0014-5793(03)01362-0
Primary Citation of Related Structures:
1UK0

PubMed Abstract:
The crystal structure of human recombinant poly(ADP-ribose) polymerase (PARP) complexed with a potent inhibitor, FR257517, was solved at 3.0 A resolution. The fluorophenyl part of the inhibitor induces an amazing conformational change in the active site of PARP by motion of the side chain of the amino acid, Arg878, which forms the bottom of the active site. Consequently, a corn-shaped hydrophobic subsite, which consists of the side chains of Leu769, Ile879, Pro881, and the methylene chain of Arg878, newly emerges from the well-known active site.

Organizational Affiliation

Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 5-2-3, Tokodai, Tsukuba, 300-2698, Ibaraki, Japan. takayoshi_kinoshita@po.fujisawa.co.jp

Macromolecule Content

Total Structure Weight: 79.15 kDa
Atom Count: 5,817
Modelled Residue Count: 700
Deposited Residue Count: 700
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Poly [ADP-ribose] polymerase-1	A, B	350	Homo sapiens	Mutation(s): 0 EC: 2.4.2.30
UniProt & NIH Common Fund Data Resources
Find proteins for P09874 (Homo sapiens) Explore P09874 Go to UniProtKB: P09874
PHAROS: P09874 GTEx: ENSG00000143799
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P09874
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
FRM Query on FRM Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth B]	C [auth A], D [auth B]	2-{3-[4-(4-FLUOROPHENYL)-3,6-DIHYDRO-1(2H)-PYRIDINYL]PROPYL}-8-METHYL-4(3H)-QUINAZOLINONE C₂₃ H₂₄ F N₃ O LOFDUAJQRUYHBR-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
FRM	BindingDB: 1UK0	IC50: min: 8, max: 16 (nM) from 2 assay(s)
FRM	PDBBind: 1UK0	IC50: 8 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.246
R-Value Work: 0.219
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 179.82	α = 90
b = 53.55	β = 114.4
c = 92.01	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing
CNX	refinement

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2004-01-27

Deposition Author(s):

Kinoshita, T.

Revision History (Full details and data files)

Version 1.0: 2004-01-27
Type: Initial release
Version 1.1: 2008-04-27
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2023-12-27
Changes: Data collection, Database references, Derived calculations