3DB8

Crystal structure of an activated (Thr->Asp) Polo-like kinase 1 (Plk1) catalytic domain in complex with Compound 041

PDB DOI: https://doi.org/10.2210/pdb3DB8/pdb

Classification: TRANSFERASE
Organism(s): Danio rerio
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2008-05-30 Released: 2008-10-07
Deposition Author(s): Elling, R.A., Hanan, E.J., Lew, W., Romanowski, M.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.15 Å
R-Value Free: 0.274
R-Value Work: 0.226
R-Value Observed: 0.232

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors.

Hanan, E.J., Fucini, R.V., Romanowski, M.J., Elling, R.A., Lew, W., Purkey, H.E., VanderPorten, E.C., Yang, W.

(2008) Bioorg Med Chem Lett 18: 5186-5189

PubMed: 18790636 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2008.08.091
Primary Citation of Related Structures:
3DB8

PubMed Abstract:
A series of 2-amino-isoxazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors. Key SAR and crystallographic data are discussed. More advanced analogues inhibit Plk1 with good enzymatic activity and modest cell-based activity. Differential selectivity among the three Plk isoforms is observed.

Organizational Affiliation

Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard Suite 400, South San Francisco, CA 94080, USA. info@sunesis.com

Macromolecule Content

Total Structure Weight: 36.4 kDa
Atom Count: 2,110
Modelled Residue Count: 261
Deposited Residue Count: 317
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Polo-like kinase 1	A	317	Danio rerio	Mutation(s): 1 Gene Names: plk1 EC: 2.7.11.21
UniProt
Find proteins for Q4KMI8 (Danio rerio) Explore Q4KMI8 Go to UniProtKB: Q4KMI8
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q4KMI8
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
1FR Query on 1FR Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	3-[3-chloro-5-(5-{[(1S)-1-phenylethyl]amino}isoxazolo[5,4-c]pyridin-3-yl)phenyl]propan-1-ol C₂₃ H₂₂ Cl N₃ O₂ MMGKIHLBFPJYJL-HNNXBMFYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
1FR	PDBBind: 3DB8	IC50: 99 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.15 Å
R-Value Free: 0.274
R-Value Work: 0.226
R-Value Observed: 0.232
Space Group: I 2 3

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 135.118	α = 90
b = 135.118	β = 90
c = 135.118	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
ADSC	data collection
MOSFLM	data reduction
SCALA	data scaling
MOLREP	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2008-10-07

Deposition Author(s):

Romanowski, M.J.

Revision History (Full details and data files)

Version 1.0: 2008-10-07
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2021-10-20
Changes: Database references, Derived calculations
Version 1.3: 2023-08-30
Changes: Data collection, Refinement description

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.