5ONE

Crystal structure of Aurora-A in complex with FMF-03-145-1 (compound 2)

PDB DOI: https://doi.org/10.2210/pdb5ONE/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2017-08-03 Released: 2017-09-06
Deposition Author(s): Chaikuad, A., Ferguson, F.M., Gray, N.S., Knapp, S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.260
R-Value Work: 0.208
R-Value Observed: 0.211

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Characterization of a highly selective inhibitor of the Aurora kinases.

Ferguson, F.M., Doctor, Z.M., Chaikuad, A., Sim, T., Kim, N.D., Knapp, S., Gray, N.S.

(2017) Bioorg Med Chem Lett 27: 4405-4408

PubMed: 28818446 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2017.08.016
Primary Citation of Related Structures:
5ONE

PubMed Abstract:
Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.

Organizational Affiliation

Department of Cancer Biology, Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

Macromolecule Content

Total Structure Weight: 33.48 kDa
Atom Count: 2,125
Modelled Residue Count: 257
Deposited Residue Count: 285
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Aurora kinase A	A	285	Homo sapiens	Mutation(s): 0 Gene Names: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O14965 (Homo sapiens) Explore O14965 Go to UniProtKB: O14965
PHAROS: O14965 GTEx: ENSG00000087586
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O14965
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
9YQ Query on 9YQ Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	4-(propanoylamino)-~{N}-[4-[(5,8,11-trimethyl-6-oxidanylidene-pyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]phenyl]benzamide C₃₀ H₂₉ N₇ O₃ KGXBCWANASZZQG-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
9YQ	BindingDB: 5ONE	IC50: 52 (nM) from 1 assay(s)
9YQ	BindingDB: 5ONE	EC50: 38 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.260
R-Value Work: 0.208
R-Value Observed: 0.211
Space Group: P 3₂ 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 86.765	α = 90
b = 86.765	β = 90
c = 77.103	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2017-09-06

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2017-09-06
Type: Initial release
Version 1.1: 2017-09-20
Changes: Database references
Version 1.2: 2024-01-17
Changes: Data collection, Database references, Refinement description