skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Dynamics of human protein kinase Aurora A linked to drug selectivity

Abstract

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1];  [2]; ORCiD logo [1]
  1. Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States
  2. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States
Publication Date:
Research Org.:
Brandeis Univ., Waltham, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
OSTI Identifier:
1454323
Alternate Identifier(s):
OSTI ID: 1454324; OSTI ID: 1509825
Grant/Contract Number:  
FG02-05ER15699; AC02-05CH11231; GM100966-01
Resource Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Name: eLife Journal Volume: 7; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Pitsawong, Warintra, Buosi, Vanessa, Otten, Renee, Agafonov, Roman V., Zorba, Adelajda, Kern, Nadja, Kutter, Steffen, Kern, Gunther, Pádua, Ricardo AP, Meniche, Xavier, and Kern, Dorothee. Dynamics of human protein kinase Aurora A linked to drug selectivity. United States: N. p., 2018. Web. doi:10.7554/eLife.36656.
Pitsawong, Warintra, Buosi, Vanessa, Otten, Renee, Agafonov, Roman V., Zorba, Adelajda, Kern, Nadja, Kutter, Steffen, Kern, Gunther, Pádua, Ricardo AP, Meniche, Xavier, & Kern, Dorothee. Dynamics of human protein kinase Aurora A linked to drug selectivity. United States. doi:10.7554/eLife.36656.
Pitsawong, Warintra, Buosi, Vanessa, Otten, Renee, Agafonov, Roman V., Zorba, Adelajda, Kern, Nadja, Kutter, Steffen, Kern, Gunther, Pádua, Ricardo AP, Meniche, Xavier, and Kern, Dorothee. Thu . "Dynamics of human protein kinase Aurora A linked to drug selectivity". United States. doi:10.7554/eLife.36656.
@article{osti_1454323,
title = {Dynamics of human protein kinase Aurora A linked to drug selectivity},
author = {Pitsawong, Warintra and Buosi, Vanessa and Otten, Renee and Agafonov, Roman V. and Zorba, Adelajda and Kern, Nadja and Kutter, Steffen and Kern, Gunther and Pádua, Ricardo AP and Meniche, Xavier and Kern, Dorothee},
abstractNote = {Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.},
doi = {10.7554/eLife.36656},
journal = {eLife},
number = ,
volume = 7,
place = {United States},
year = {2018},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.7554/eLife.36656

Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent
journal, October 2015

  • Bavetsias, Vassilios; Pérez-Fuertes, Yolanda; McIntyre, Patrick J.
  • Bioorganic & Medicinal Chemistry Letters, Vol. 25, Issue 19
  • DOI: 10.1016/j.bmcl.2015.08.003

Aurora Kinases: New Targets for Cancer Therapy
journal, December 2006


Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain
journal, March 2010

  • Wojcik, John; Hantschel, Oliver; Grebien, Florian
  • Nature Structural & Molecular Biology, Vol. 17, Issue 4
  • DOI: 10.1038/nsmb.1793

Aurora kinase inhibitors: Progress towards the clinic
journal, February 2012

  • Kollareddy, Madhu; Zheleva, Daniella; Dzubak, Petr
  • Investigational New Drugs, Vol. 30, Issue 6
  • DOI: 10.1007/s10637-012-9798-6

Global Kinetic Explorer: A new computer program for dynamic simulation and fitting of kinetic data
journal, April 2009

  • Johnson, Kenneth A.; Simpson, Zachary B.; Blom, Thomas
  • Analytical Biochemistry, Vol. 387, Issue 1
  • DOI: 10.1016/j.ab.2008.12.024

Solution Conformations and Dynamics of ABL Kinase-Inhibitor Complexes Determined by NMR Substantiate the Different Binding Modes of Imatinib/Nilotinib and Dasatinib
journal, April 2008

  • Vajpai, Navratna; Strauss, André; Fendrich, Gabriele
  • Journal of Biological Chemistry, Vol. 283, Issue 26
  • DOI: 10.1074/jbc.M801337200

PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer
journal, December 2007


Switching Aurora-A kinase on and off at an allosteric site
journal, April 2017

  • Bayliss, Richard; Burgess, Selena G.; McIntyre, Patrick J.
  • The FEBS Journal, Vol. 284, Issue 18
  • DOI: 10.1111/febs.14069

Dynamics-Driven Allostery in Protein Kinases
journal, November 2015


Drug–target residence time and its implications for lead optimization
journal, August 2006

  • Copeland, Robert A.; Pompliano, David L.; Meek, Thomas D.
  • Nature Reviews Drug Discovery, Vol. 5, Issue 9
  • DOI: 10.1038/nrd2082

Aurora kinase inhibitors as anti-cancer therapy
journal, January 2010


Crystal Structure of Aurora-2, an Oncogenic Serine/Threonine Kinase
journal, September 2002

  • Cheetham, Graham M. T.; Knegtel, Ronald M. A.; Coll, Joyce T.
  • Journal of Biological Chemistry, Vol. 277, Issue 45
  • DOI: 10.1074/jbc.C200426200

Nmrglue: an open source Python package for the analysis of multidimensional NMR data
journal, March 2013


Ins and Outs of Kinase DFG Motifs
journal, June 2013


Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy
journal, August 2017

  • Gilburt, James A. H.; Sarkar, Hajrah; Sheldrake, Peter
  • Angewandte Chemie International Edition, Vol. 56, Issue 38
  • DOI: 10.1002/anie.201704654

Drugging MYCN through an Allosteric Transition in Aurora Kinase A
journal, September 2014

  • Gustafson, William Clay; Meyerowitz, Justin Gabriel; Nekritz, Erin A.
  • Cancer Cell, Vol. 26, Issue 3
  • DOI: 10.1016/j.ccr.2014.07.015

Small Molecule Recognition of c-Src via the Imatinib-Binding Conformation
journal, October 2008


Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012

  • Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
  • Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
  • DOI: 10.1107/S0907444912001308

Aurora kinase inhibitors as anticancer molecules
journal, October 2010

  • Katayama, Hiroshi; Sen, Subrata
  • Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Vol. 1799, Issue 10-12
  • DOI: 10.1016/j.bbagrm.2010.09.004

Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2
journal, May 2014


1,4,5,6-Tetrahydropyrrolo[3,4- c ]pyrazoles:  Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile
journal, November 2006

  • Fancelli, Daniele; Moll, Jürgen; Varasi, Mario
  • Journal of Medicinal Chemistry, Vol. 49, Issue 24
  • DOI: 10.1021/jm060897w

Phase I Pharmacokinetic and Pharmacodynamic Study of the Aurora Kinase Inhibitor Danusertib in Patients With Advanced or Metastatic Solid Tumors
journal, October 2009

  • Steeghs, Neeltje; Eskens, Ferry A. L. M.; Gelderblom, Hans
  • Journal of Clinical Oncology, Vol. 27, Issue 30
  • DOI: 10.1200/JCO.2008.21.6655

A Novel Mechanism by Which Small Molecule Inhibitors Induce the DFG Flip in Aurora A
journal, January 2012

  • Martin, Mathew P.; Zhu, Jin-Yi; Lawrence, Harshani R.
  • ACS Chemical Biology, Vol. 7, Issue 4
  • DOI: 10.1021/cb200508b

How good are my data and what is the resolution?
journal, June 2013

  • Evans, Philip R.; Murshudov, Garib N.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
  • DOI: 10.1107/S0907444913000061

Imatinib: A Breakthrough of Targeted Therapy in Cancer
journal, January 2014

  • Iqbal, Nida; Iqbal, Naveed
  • Chemotherapy Research and Practice, Vol. 2014
  • DOI: 10.1155/2014/357027

NMR Characterization of Kinase p38 Dynamics in Free and Ligand-Bound Forms
journal, January 2006

  • Vogtherr, Martin; Saxena, Krishna; Hoelder, Swen
  • Angewandte Chemie International Edition, Vol. 45, Issue 6
  • DOI: 10.1002/anie.200502770

Characterization of a highly selective inhibitor of the Aurora kinases
journal, September 2017

  • Ferguson, Fleur M.; Doctor, Zainab M.; Chaikuad, Apirat
  • Bioorganic & Medicinal Chemistry Letters, Vol. 27, Issue 18
  • DOI: 10.1016/j.bmcl.2017.08.016

Energetic dissection of Gleevec's selectivity toward human tyrosine kinases
journal, September 2014

  • Agafonov, Roman V.; Wilson, Christopher; Otten, Renee
  • Nature Structural & Molecular Biology, Vol. 21, Issue 10
  • DOI: 10.1038/nsmb.2891

Tyrosine Kinase Activation and Conformational Flexibility: Lessons from Src-Family Tyrosine Kinases
journal, April 2017


Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase
journal, September 2000


Structural Basis of Aurora-A Activation by TPX2 at the Mitotic Spindle
journal, October 2003


ACHESYM : an algorithm and server for standardized placement of macromolecular models in the unit cell
journal, November 2014

  • Kowiel, Marcin; Jaskolski, Mariusz; Dauter, Zbigniew
  • Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 12
  • DOI: 10.1107/S1399004714024572

Aurora-A — A guardian of poles
journal, January 2005

  • Marumoto, Tomotoshi; Zhang, Dongwei; Saya, Hideyuki
  • Nature Reviews Cancer, Vol. 5, Issue 1
  • DOI: 10.1038/nrc1526

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors
journal, July 2015


XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/S0907444909047337

A dynamic mechanism for allosteric activation of Aurora kinase A by activation loop phosphorylation
journal, February 2018

  • Ruff, Emily F.; Muretta, Joseph M.; Thompson, Andrew R.
  • eLife, Vol. 7
  • DOI: 10.7554/eLife.32766

Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance
journal, February 2017

  • Willemsen-Seegers, Nicole; Uitdehaag, Joost C. M.; Prinsen, Martine B. W.
  • Journal of Molecular Biology, Vol. 429, Issue 4
  • DOI: 10.1016/j.jmb.2016.12.019

Structures of the Cancer-Related Aurora-A, FAK, and EphA2 Protein Kinases from Nanovolume Crystallography
journal, December 2002


UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

Modulation of kinase-inhibitor interactions by auxiliary protein binding: Crystallography studies on Aurora A interactions with VX-680 and with TPX2
journal, October 2008

  • Zhao, Baoguang; Smallwood, Angela; Yang, Jingsong
  • Protein Science, Vol. 17, Issue 10
  • DOI: 10.1110/ps.036590.108

Activation pathway of Src kinase reveals intermediate states as targets for drug design
journal, March 2014

  • Shukla, Diwakar; Meng, Yilin; Roux, Benoît
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms4397

Aurora Kinase Inhibitors: Current Status and Outlook
journal, December 2015


Crystal structure of an Aurora-A mutant that mimics Aurora-B bound to MLN8054: insights into selectivity and drug design
journal, March 2010

  • Dodson, Charlotte A.; Kosmopoulou, Magda; Richards, Mark W.
  • Biochemical Journal, Vol. 427, Issue 1
  • DOI: 10.1042/BJ20091530

Improved low-resolution crystallographic refinement with Phenix and Rosetta
journal, September 2013

  • DiMaio, Frank; Echols, Nathaniel; Headd, Jeffrey J.
  • Nature Methods, Vol. 10, Issue 11
  • DOI: 10.1038/nmeth.2648

Unactivated PKR Exists in an Open Conformation Capable of Binding Nucleotides
journal, August 2006

  • Lemaire, Peter A.; Tessmer, Ingrid; Craig, Ranyelle
  • Biochemistry, Vol. 45, Issue 30
  • DOI: 10.1021/bi060567d

Characterization of Three Druggable Hot-Spots in the Aurora-A/TPX2 Interaction Using Biochemical, Biophysical, and Fragment-Based Approaches
journal, October 2017

  • McIntyre, Patrick J.; Collins, Patrick M.; Vrzal, Lukáš
  • ACS Chemical Biology, Vol. 12, Issue 11
  • DOI: 10.1021/acschembio.7b00537

Computational Study of the “DFG-Flip” Conformational Transition in c-Abl and c-Src Tyrosine Kinases
journal, January 2015

  • Meng, Yilin; Lin, Yen-lin; Roux, Benoît
  • The Journal of Physical Chemistry B, Vol. 119, Issue 4
  • DOI: 10.1021/jp511792a

Identification of a Major Determinant for Serine-Threonine Kinase Phosphoacceptor Specificity
journal, January 2014


iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM
journal, March 2011

  • Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910048675

Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2
journal, June 2016

  • Janeček, Matej; Rossmann, Maxim; Sharma, Pooja
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep28528

c-Src Binds to the Cancer Drug Imatinib with an Inactive Abl/c-Kit Conformation and a Distributed Thermodynamic Penalty
journal, March 2007


xia2 : an expert system for macromolecular crystallography data reduction
journal, December 2009


The druggable genome
journal, September 2002

  • Hopkins, Andrew L.; Groom, Colin R.
  • Nature Reviews Drug Discovery, Vol. 1, Issue 9
  • DOI: 10.1038/nrd892

Protein kinases — the major drug targets of the twenty-first century?
journal, April 2002

  • Cohen, Philip
  • Nature Reviews Drug Discovery, Vol. 1, Issue 4
  • DOI: 10.1038/nrd773

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

The Different Flexibility of c-Src and c-Abl Kinases Regulates the Accessibility of a Druggable Inactive Conformation
journal, January 2012

  • Lovera, Silvia; Sutto, Ludovico; Boubeva, Ralitza
  • Journal of the American Chemical Society, Vol. 134, Issue 5
  • DOI: 10.1021/ja210751t

Structure-kinetic relationship study of CDK8/CycC specific compounds
journal, April 2013

  • Schneider, E. V.; Bottcher, J.; Huber, R.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 20
  • DOI: 10.1073/pnas.1305378110

Equally Potent Inhibition of c-Src and Abl by Compounds that Recognize Inactive Kinase Conformations
journal, March 2009


Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Insights into nucleotide binding in protein kinase A using fluorescent adenosine derivatives
journal, January 2000

  • Ni, Da Qun; Shaffer, Jennifer; Adams, Joseph A.
  • Protein Science, Vol. 9, Issue 9
  • DOI: 10.1110/ps.9.9.1818

Simple and inexpensive incorporation of 19F-Tryptophan for protein NMR spectroscopy
journal, January 2012

  • Crowley, Peter B.; Kyne, Ciara; Monteith, William B.
  • Chemical Communications, Vol. 48, Issue 86
  • DOI: 10.1039/c2cc35347d

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

A comprehensive review on Aurora kinase: Small molecule inhibitors and clinical trial studies
journal, November 2017


CheckMyMetal : a macromolecular metal-binding validation tool
journal, February 2017

  • Zheng, Heping; Cooper, David R.; Porebski, Przemyslaw J.
  • Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 3
  • DOI: 10.1107/S2059798317001061

SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors
journal, March 2006

  • Heron, Nicola M.; Anderson, Malcolm; Blowers, David P.
  • Bioorganic & Medicinal Chemistry Letters, Vol. 16, Issue 5
  • DOI: 10.1016/j.bmcl.2005.11.053

Fragment-Based Discovery of the Pyrazol-4-yl Urea (AT9283), a Multitargeted Kinase Inhibitor with Potent Aurora Kinase Activity
journal, January 2009

  • Howard, Steven; Berdini, Valerio; Boulstridge, John A.
  • Journal of Medicinal Chemistry, Vol. 52, Issue 2
  • DOI: 10.1021/jm800984v

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain
journal, May 2006


Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain
journal, July 2016

  • Burgess, Selena G.; Oleksy, Arkadiusz; Cavazza, Tommaso
  • Open Biology, Vol. 6, Issue 7
  • DOI: 10.1098/rsob.160089

A water-mediated allosteric network governs activation of Aurora kinase A
journal, February 2017

  • Cyphers, Soreen; Ruff, Emily F.; Behr, Julie M.
  • Nature Chemical Biology, Vol. 13, Issue 4
  • DOI: 10.1038/nchembio.2296

Backbone assignment of the tyrosine kinase Src catalytic domain in complex with imatinib
journal, April 2011

  • Campos-Olivas, Ramón; Marenchino, Marco; Scapozza, Leonardo
  • Biomolecular NMR Assignments, Vol. 5, Issue 2
  • DOI: 10.1007/s12104-011-9304-7

Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening
journal, March 2016


Aurora A kinase (AURKA) in normal and pathological cell division
journal, August 2012

  • Nikonova, Anna S.; Astsaturov, Igor; Serebriiskii, Ilya G.
  • Cellular and Molecular Life Sciences, Vol. 70, Issue 4
  • DOI: 10.1007/s00018-012-1073-7

Aurora Kinases as Anticancer Drug Targets
journal, March 2008


Roles of Aurora Kinases in Mitosis and Tumorigenesis
journal, January 2007


NMRPipe: A multidimensional spectral processing system based on UNIX pipes
journal, November 1995

  • Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW.
  • Journal of Biomolecular NMR, Vol. 6, Issue 3
  • DOI: 10.1007/BF00197809

The drug–target residence time model: a 10-year retrospective
journal, December 2015


Defining the conserved internal architecture of a protein kinase
journal, March 2010

  • Kornev, Alexandr P.; Taylor, Susan S.
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 3
  • DOI: 10.1016/j.bbapap.2009.10.017

Aurora A, centrosome structure, and the centrosome cycle
journal, October 2009

  • Lukasiewicz, Kara B.; Lingle, Wilma L.
  • Environmental and Molecular Mutagenesis, Vol. 50, Issue 8
  • DOI: 10.1002/em.20533

Antimitotic drugs in cancer chemotherapy: Promises and pitfalls
journal, September 2013


Rational design of inhibitors that bind to inactive kinase conformations
journal, June 2006

  • Liu, Yi; Gray, Nathanael S.
  • Nature Chemical Biology, Vol. 2, Issue 7
  • DOI: 10.1038/nchembio799

Evolution of the eukaryotic protein kinases as dynamic molecular switches
journal, September 2012

  • Taylor, Susan S.; Keshwani, Malik M.; Steichen, Jon M.
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 367, Issue 1602
  • DOI: 10.1098/rstb.2012.0054

Using ancient protein kinases to unravel a modern cancer drug's mechanism
journal, February 2015


A Computational Model for Overcoming Drug Resistance Using Selective Dual-Inhibitors for Aurora Kinase A and Its T217D Variant
journal, November 2013

  • Barakat, Khaled H.; Huzil, J. Torin; Jordan, Kirk E.
  • Molecular Pharmaceutics, Vol. 10, Issue 12
  • DOI: 10.1021/mp4003893

Three-dimensional structure of the tyrosine kinase c-Src
journal, February 1997

  • Xu, Wenqing; Harrison, Stephen C.; Eck, Michael J.
  • Nature, Vol. 385, Issue 6617
  • DOI: 10.1038/385595a0

Disabling ErbB Receptors with Rationally Designed Exocyclic Mimetics of Antibodies:  Structure−Function Analysis
journal, August 2001

  • Berezov, Alan; Zhang, Hong-Tao; Greene, Mark I.
  • Journal of Medicinal Chemistry, Vol. 44, Issue 16
  • DOI: 10.1021/jm000527m

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Identification of small molecule inhibitors of the Aurora-A/TPX2 complex
journal, March 2017


Current applications of 19F NMR to studies of protein structure and dynamics
journal, April 2012

  • Kitevski-LeBlanc, Julianne L.; Prosser, R. Scott
  • Progress in Nuclear Magnetic Resonance Spectroscopy, Vol. 62
  • DOI: 10.1016/j.pnmrs.2011.06.003