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Title: Allosteric activation of apicomplexan calcium-dependent protein kinases

Abstract

Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca 2+-regulated kinases in plants and protists. It has long been assumed that CDPKs are activated, like other Ca 2+-regulated kinases, by derepression of the kinase domain (KD). However, we found that removal of the autoinhibitory domain from Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We uncovered the molecular basis for this inhibition by solving the crystal structure of the complex and simulating, through molecular dynamics, the effects of 1B7–kinase interactions. In contrast to other Ca 2+-regulated kinases, the regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the kinase in response to changes in Ca 2+ concentrations. We propose that the regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the otherwise inactive KD. This dependence on allosteric stabilization reveals a novel susceptibility in this important class of parasite enzymes.

Authors:
 [1];  [2];  [1];  [1];  [3];  [3];  [4];  [2];  [5]; ORCiD logo [1]
  1. Whitehead Inst. for Biomedical Research, Cambridge, MA (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Biology
  3. D. E. Shaw Research, New York, NY (United States)
  4. D. E. Shaw Research, New York, NY (United States); Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics
  5. Whitehead Inst. for Biomedical Research, Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Biology
Publication Date:
Research Org.:
Whitehead Inst. for Biomedical Research, Cambridge, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States); National Science Foundation (NSF); German Academic Exchange Service (Germany)
Contributing Org.:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); D. E. Shaw Research, New York, NY (United States); Columbia Univ., New York, NY (United States)
OSTI Identifier:
1214843
Grant/Contract Number:  
AC02-06CH11357; GM103403; T32GM007287; 1122374; 1DP5OD017892
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 112; Journal Issue: 36; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; calcium-dependent protein kinase; kinase activation; VHH

Citation Formats

Ingram, Jessica R., Knockenhauer, Kevin E., Markus, Benedikt M., Mandelbaum, Joseph, Ramek, Alexander, Shan, Yibing, Shaw, David E., Schwartz, Thomas U., Ploegh, Hidde L., and Lourido, Sebastian. Allosteric activation of apicomplexan calcium-dependent protein kinases. United States: N. p., 2015. Web. doi:10.1073/pnas.1505914112.
Ingram, Jessica R., Knockenhauer, Kevin E., Markus, Benedikt M., Mandelbaum, Joseph, Ramek, Alexander, Shan, Yibing, Shaw, David E., Schwartz, Thomas U., Ploegh, Hidde L., & Lourido, Sebastian. Allosteric activation of apicomplexan calcium-dependent protein kinases. United States. doi:10.1073/pnas.1505914112.
Ingram, Jessica R., Knockenhauer, Kevin E., Markus, Benedikt M., Mandelbaum, Joseph, Ramek, Alexander, Shan, Yibing, Shaw, David E., Schwartz, Thomas U., Ploegh, Hidde L., and Lourido, Sebastian. Mon . "Allosteric activation of apicomplexan calcium-dependent protein kinases". United States. doi:10.1073/pnas.1505914112. https://www.osti.gov/servlets/purl/1214843.
@article{osti_1214843,
title = {Allosteric activation of apicomplexan calcium-dependent protein kinases},
author = {Ingram, Jessica R. and Knockenhauer, Kevin E. and Markus, Benedikt M. and Mandelbaum, Joseph and Ramek, Alexander and Shan, Yibing and Shaw, David E. and Schwartz, Thomas U. and Ploegh, Hidde L. and Lourido, Sebastian},
abstractNote = {Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca2+-regulated kinases in plants and protists. It has long been assumed that CDPKs are activated, like other Ca2+-regulated kinases, by derepression of the kinase domain (KD). However, we found that removal of the autoinhibitory domain from Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We uncovered the molecular basis for this inhibition by solving the crystal structure of the complex and simulating, through molecular dynamics, the effects of 1B7–kinase interactions. In contrast to other Ca2+-regulated kinases, the regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the kinase in response to changes in Ca2+ concentrations. We propose that the regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the otherwise inactive KD. This dependence on allosteric stabilization reveals a novel susceptibility in this important class of parasite enzymes.},
doi = {10.1073/pnas.1505914112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 36,
volume = 112,
place = {United States},
year = {2015},
month = {8}
}

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Cited by: 14 works
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Works referenced in this record:

X-Ray Diffraction data from CDPK1, from Toxoplasma gondii, bound to inhibitory VHH-1B7 , source of 4YGA structure [Supplemental Data]
dataset, December 2013

  • Knockenhauer, Kevin E.; Schwartz, Thomas
  • SBGrid Data Bank, Multiple files (4.7 G)
  • DOI: 10.15785/sbgrid/219

X-Ray Diffraction data from CDPK1, from Toxoplasma gondii, bound to inhibitory VHH-1B7, source of 4YGA structure
dataset, January 2016


Loops, Linkages, Rings, Catenanes, Cages, and Crowders:  Entropy-Based Strategies for Stabilizing Proteins
journal, February 2004

  • Zhou, Huan-Xiang
  • Accounts of Chemical Research, Vol. 37, Issue 2
  • DOI: 10.1021/ar0302282

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

Oncogenic Mutations Counteract Intrinsic Disorder in the EGFR Kinase and Promote Receptor Dimerization
journal, May 2012


Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium
journal, May 2010

  • Wernimont, Amy K.; Artz, Jennifer D.; Finerty, Patrick
  • Nature Structural & Molecular Biology, Vol. 17, Issue 5
  • DOI: 10.1038/nsmb.1795

TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells
journal, December 2012


Structure of the Regulatory Apparatus of a Calcium-dependent Protein Kinase (CDPK): A Novel Mode of Calmodulin-target Recognition
journal, March 2006

  • Chandran, Vidya; Stollar, Elliott J.; Lindorff-Larsen, Kresten
  • Journal of Molecular Biology, Vol. 357, Issue 2
  • DOI: 10.1016/j.jmb.2005.11.093

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp
journal, March 2015


Collaboration gets the most out of software
journal, September 2013


Improved side-chain torsion potentials for the Amber ff99SB protein force field
journal, January 2010

  • Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim
  • Proteins: Structure, Function, and Bioinformatics
  • DOI: 10.1002/prot.22711

Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria.
journal, December 1993

  • Donald, R. G.; Roos, D. S.
  • Proceedings of the National Academy of Sciences, Vol. 90, Issue 24
  • DOI: 10.1073/pnas.90.24.11703

Optimized Molecular Dynamics Force Fields Applied to the Helix−Coil Transition of Polypeptides
journal, July 2009

  • Best, Robert B.; Hummer, Gerhard
  • The Journal of Physical Chemistry B, Vol. 113, Issue 26
  • DOI: 10.1021/jp901540t

Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase
journal, March 2003


A common, avoidable source of error in molecular dynamics integrators
journal, January 2007

  • Lippert, Ross A.; Bowers, Kevin J.; Dror, Ron O.
  • The Journal of Chemical Physics, Vol. 126, Issue 4
  • DOI: 10.1063/1.2431176

Comparison of simple potential functions for simulating liquid water
journal, July 1983

  • Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
  • The Journal of Chemical Physics, Vol. 79, Issue 2
  • DOI: 10.1063/1.445869

Dissection of Mechanisms Involved in the Regulation of Plasmodium falciparum Calcium-dependent Protein Kinase 4
journal, March 2009

  • Ranjan, Ravikant; Ahmed, Anwar; Gourinath, Samudrala
  • Journal of Biological Chemistry, Vol. 284, Issue 22
  • DOI: 10.1074/jbc.M900656200

A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations
journal, January 2001


Reversible multiple time scale molecular dynamics
journal, August 1992

  • Tuckerman, M.; Berne, B. J.; Martyna, G. J.
  • The Journal of Chemical Physics, Vol. 97, Issue 3
  • DOI: 10.1063/1.463137

Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies
journal, March 2006

  • De Genst, E.; Silence, K.; Decanniere, K.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 12
  • DOI: 10.1073/pnas.0505379103

Comparison of multiple Amber force fields and development of improved protein backbone parameters
journal, November 2006

  • Hornak, Viktor; Abel, Robert; Okur, Asim
  • Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3
  • DOI: 10.1002/prot.21123

Participation of myosin in gliding motility and host cell invasion by Toxoplasma gondii
journal, October 1997


Regulation of the p85/p110 Phosphatidylinositol 3′-Kinase: Stabilization and Inhibition of the p110α Catalytic Subunit by the p85 Regulatory Subunit
journal, March 1998

  • Yu, Jinghua; Zhang, Yitao; McIlroy, James
  • Molecular and Cellular Biology, Vol. 18, Issue 3
  • DOI: 10.1128/MCB.18.3.1379

A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
journal, May 1995

  • Cornell, Wendy D.; Cieplak, Piotr; Bayly, Christopher I.
  • Journal of the American Chemical Society, Vol. 117, Issue 19
  • DOI: 10.1021/ja00124a002

Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007


A Novel Calcium-Dependent Protein Kinase Inhibitor as a Lead Compound for Treating Cryptosporidiosis
journal, July 2013

  • Castellanos-Gonzalez, Alejandro; White, A. Clinton; Ojo, Kayode K.
  • The Journal of Infectious Diseases, Vol. 208, Issue 8
  • DOI: 10.1093/infdis/jit327

Inhibition of Plasmodium falciparum CDPK1 by conditional expression of its J-domain demonstrates a key role in schizont development
journal, May 2013

  • Azevedo, Mauro F.; Sanders, Paul R.; Krejany, Efrosinia
  • Biochemical Journal, Vol. 452, Issue 3
  • DOI: 10.1042/BJ20130124

Evidence for Differing Roles for Each Lobe of the Calmodulin-like Domain in a Calcium-dependent Protein Kinase
journal, May 2004

  • Christodoulou, John; Malmendal, Anders; Harper, Jeffrey F.
  • Journal of Biological Chemistry, Vol. 279, Issue 28
  • DOI: 10.1074/jbc.M401297200

Gaussian split Ewald: A fast Ewald mesh method for molecular simulation
journal, February 2005

  • Shan, Yibing; Klepeis, John L.; Eastwood, Michael P.
  • The Journal of Chemical Physics, Vol. 122, Issue 5
  • DOI: 10.1063/1.1839571

Nanobody-based products as research and diagnostic tools
journal, May 2014


A Forward Genetic Screen Reveals that Calcium-dependent Protein Kinase 3 Regulates Egress in Toxoplasma
journal, November 2012


Optimized E. coli expression strain LOBSTR eliminates common contaminants from His-tag purification : Optimized
journal, August 2013

  • Andersen, Kasper R.; Leksa, Nina C.; Schwartz, Thomas U.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 81, Issue 11
  • DOI: 10.1002/prot.24364

Structure of the Autoinhibited Kinase Domain of CaMKII and SAXS Analysis of the Holoenzyme
journal, December 2005


Distinct signalling pathways control Toxoplasma egress and host-cell invasion : Distinct signalling pathways control
journal, November 2012

  • Lourido, Sebastian; Tang, Keliang; Sibley, L. David
  • The EMBO Journal, Vol. 31, Issue 24
  • DOI: 10.1038/emboj.2012.299

Structure of the CaMKIIδ/Calmodulin Complex Reveals the Molecular Mechanism of CaMKII Kinase Activation
journal, July 2010


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

Alpaca (Lama pacos) as a convenient source of recombinant camelid heavy chain antibodies (VHHs)
journal, July 2007

  • Maass, David R.; Sepulveda, Jorge; Pernthaner, Anton
  • Journal of Immunological Methods, Vol. 324, Issue 1-2
  • DOI: 10.1016/j.jim.2007.04.008

Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors
journal, May 2010

  • Ojo, Kayode K.; Larson, Eric T.; Keyloun, Katelyn R.
  • Nature Structural & Molecular Biology, Vol. 17, Issue 5
  • DOI: 10.1038/nsmb.1818

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

Catalytic Control in the EGF Receptor and Its Connection to General Kinase Regulatory Mechanisms
journal, April 2011


Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors
journal, June 2012

  • Ojo, Kayode K.; Pfander, Claudia; Mueller, Natascha R.
  • Journal of Clinical Investigation, Vol. 122, Issue 6
  • DOI: 10.1172/JCI61822

Canonical dynamics: Equilibrium phase-space distributions
journal, March 1985


Novel insights into the regulation of malarial calcium-dependent protein kinase 1
journal, August 2012

  • Ahmed, Anwar; Gaadhe, Kavita; Sharma, Guru Prasad
  • The FASEB Journal, Vol. 26, Issue 8
  • DOI: 10.1096/fj.12-203877

Dimerization-Induced Activation of Soluble Insulin/IGF-1 Receptor Kinases:  An Alternative Mechanism of Activation
journal, November 2001

  • Baer, Kristin; Al-Hasani, Hadi; Parvaresch, Susan
  • Biochemistry, Vol. 40, Issue 47
  • DOI: 10.1021/bi015588g

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

Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma
journal, May 2010

  • Lourido, Sebastian; Shuman, Joel; Zhang, Chao
  • Nature, Vol. 465, Issue 7296
  • DOI: 10.1038/nature09022

Jalview Version 2--a multiple sequence alignment editor and analysis workbench
journal, January 2009


Exploiting the Unique ATP-Binding Pocket of Toxoplasma Calcium-Dependent Protein Kinase 1 To Identify Its Substrates
journal, April 2013

  • Lourido, Sebastian; Jeschke, Grace R.; Turk, Benjamin E.
  • ACS Chemical Biology, Vol. 8, Issue 6
  • DOI: 10.1021/cb400115y

Pseudosubstrate Inhibition of CDPK, a Protein Kinase with a Calmodulin-like Domain
journal, June 1994

  • Harmon, Alice C.; Yoo, Byung-Chun; McCaffery, Candace
  • Biochemistry, Vol. 33, Issue 23
  • DOI: 10.1021/bi00189a032

Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation
journal, September 2008


Genetic Identification of an Autoinhibitor in CDPK, a Protein Kinase with a Calmodulin-like Domain
journal, June 1994

  • Harper, Jeffrey F.; Huang, Jing-Feng; Lloyd, S. Jane
  • Biochemistry, Vol. 33, Issue 23
  • DOI: 10.1021/bi00189a031

X-Ray Diffraction data from CDPK1, from Toxoplasma gondii, bound to inhibitory VHH-1B7 , source of 4YGA structure [Supplemental Data]
dataset, December 2013

  • Knockenhauer, Kevin E.; Schwartz, Thomas
  • SBGrid Data Bank, Multiple files (4.7 G)
  • DOI: 10.15785/sbgrid/219

    Works referencing / citing this record:

    X-Ray Diffraction data from CDPK1, from Toxoplasma gondii, bound to inhibitory VHH-1B7 , source of 4YGA structure [Supplemental Data]
    dataset, December 2013

    • Knockenhauer, Kevin E.; Schwartz, Thomas
    • SBGrid Data Bank, Multiple files (4.7 G)
    • DOI: 10.15785/sbgrid/219

    X-Ray Diffraction data from CDPK1, from Toxoplasma gondii, bound to inhibitory VHH-1B7, source of 4YGA structure
    dataset, January 2016


    Comparison of multiple Amber force fields and development of improved protein backbone parameters
    journal, November 2006

    • Hornak, Viktor; Abel, Robert; Okur, Asim
    • Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3
    • DOI: 10.1002/prot.21123

    Improved side-chain torsion potentials for the Amber ff99SB protein force field
    journal, January 2010

    • Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim
    • Proteins: Structure, Function, and Bioinformatics
    • DOI: 10.1002/prot.22711

    Optimized E. coli expression strain LOBSTR eliminates common contaminants from His-tag purification : Optimized
    journal, August 2013

    • Andersen, Kasper R.; Leksa, Nina C.; Schwartz, Thomas U.
    • Proteins: Structure, Function, and Bioinformatics, Vol. 81, Issue 11
    • DOI: 10.1002/prot.24364

    The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp
    journal, March 2015


    Structure of the Autoinhibited Kinase Domain of CaMKII and SAXS Analysis of the Holoenzyme
    journal, December 2005


    Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation
    journal, September 2008


    Oncogenic Mutations Counteract Intrinsic Disorder in the EGFR Kinase and Promote Receptor Dimerization
    journal, May 2012


    Alpaca (Lama pacos) as a convenient source of recombinant camelid heavy chain antibodies (VHHs)
    journal, July 2007

    • Maass, David R.; Sepulveda, Jorge; Pernthaner, Anton
    • Journal of Immunological Methods, Vol. 324, Issue 1-2
    • DOI: 10.1016/j.jim.2007.04.008

    Structure of the Regulatory Apparatus of a Calcium-dependent Protein Kinase (CDPK): A Novel Mode of Calmodulin-target Recognition
    journal, March 2006

    • Chandran, Vidya; Stollar, Elliott J.; Lindorff-Larsen, Kresten
    • Journal of Molecular Biology, Vol. 357, Issue 2
    • DOI: 10.1016/j.jmb.2005.11.093

    Inference of Macromolecular Assemblies from Crystalline State
    journal, September 2007


    Catalytic Control in the EGF Receptor and Its Connection to General Kinase Regulatory Mechanisms
    journal, April 2011


    Nanobody-based products as research and diagnostic tools
    journal, May 2014


    Loops, Linkages, Rings, Catenanes, Cages, and Crowders:  Entropy-Based Strategies for Stabilizing Proteins
    journal, February 2004

    • Zhou, Huan-Xiang
    • Accounts of Chemical Research, Vol. 37, Issue 2
    • DOI: 10.1021/ar0302282

    Genetic Identification of an Autoinhibitor in CDPK, a Protein Kinase with a Calmodulin-like Domain
    journal, June 1994

    • Harper, Jeffrey F.; Huang, Jing-Feng; Lloyd, S. Jane
    • Biochemistry, Vol. 33, Issue 23
    • DOI: 10.1021/bi00189a031

    Pseudosubstrate Inhibition of CDPK, a Protein Kinase with a Calmodulin-like Domain
    journal, June 1994

    • Harmon, Alice C.; Yoo, Byung-Chun; McCaffery, Candace
    • Biochemistry, Vol. 33, Issue 23
    • DOI: 10.1021/bi00189a032

    Dimerization-Induced Activation of Soluble Insulin/IGF-1 Receptor Kinases:  An Alternative Mechanism of Activation
    journal, November 2001

    • Baer, Kristin; Al-Hasani, Hadi; Parvaresch, Susan
    • Biochemistry, Vol. 40, Issue 47
    • DOI: 10.1021/bi015588g

    Exploiting the Unique ATP-Binding Pocket of Toxoplasma Calcium-Dependent Protein Kinase 1 To Identify Its Substrates
    journal, April 2013

    • Lourido, Sebastian; Jeschke, Grace R.; Turk, Benjamin E.
    • ACS Chemical Biology, Vol. 8, Issue 6
    • DOI: 10.1021/cb400115y

    A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
    journal, May 1995

    • Cornell, Wendy D.; Cieplak, Piotr; Bayly, Christopher I.
    • Journal of the American Chemical Society, Vol. 117, Issue 19
    • DOI: 10.1021/ja00124a002

    Optimized Molecular Dynamics Force Fields Applied to the Helix−Coil Transition of Polypeptides
    journal, July 2009

    • Best, Robert B.; Hummer, Gerhard
    • The Journal of Physical Chemistry B, Vol. 113, Issue 26
    • DOI: 10.1021/jp901540t

    Distinct signalling pathways control Toxoplasma egress and host-cell invasion : Distinct signalling pathways control
    journal, November 2012

    • Lourido, Sebastian; Tang, Keliang; Sibley, L. David
    • The EMBO Journal, Vol. 31, Issue 24
    • DOI: 10.1038/emboj.2012.299

    Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma
    journal, May 2010

    • Lourido, Sebastian; Shuman, Joel; Zhang, Chao
    • Nature, Vol. 465, Issue 7296
    • DOI: 10.1038/nature09022

    Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium
    journal, May 2010

    • Wernimont, Amy K.; Artz, Jennifer D.; Finerty, Patrick
    • Nature Structural & Molecular Biology, Vol. 17, Issue 5
    • DOI: 10.1038/nsmb.1795

    Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors
    journal, May 2010

    • Ojo, Kayode K.; Larson, Eric T.; Keyloun, Katelyn R.
    • Nature Structural & Molecular Biology, Vol. 17, Issue 5
    • DOI: 10.1038/nsmb.1818

    Participation of myosin in gliding motility and host cell invasion by Toxoplasma gondii
    journal, October 1997


    Gaussian split Ewald: A fast Ewald mesh method for molecular simulation
    journal, February 2005

    • Shan, Yibing; Klepeis, John L.; Eastwood, Michael P.
    • The Journal of Chemical Physics, Vol. 122, Issue 5
    • DOI: 10.1063/1.1839571

    A common, avoidable source of error in molecular dynamics integrators
    journal, January 2007

    • Lippert, Ross A.; Bowers, Kevin J.; Dror, Ron O.
    • The Journal of Chemical Physics, Vol. 126, Issue 4
    • DOI: 10.1063/1.2431176

    Comparison of simple potential functions for simulating liquid water
    journal, July 1983

    • Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
    • The Journal of Chemical Physics, Vol. 79, Issue 2
    • DOI: 10.1063/1.445869

    Reversible multiple time scale molecular dynamics
    journal, August 1992

    • Tuckerman, M.; Berne, B. J.; Martyna, G. J.
    • The Journal of Chemical Physics, Vol. 97, Issue 3
    • DOI: 10.1063/1.463137

    Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies
    journal, March 2006

    • De Genst, E.; Silence, K.; Decanniere, K.
    • Proceedings of the National Academy of Sciences, Vol. 103, Issue 12
    • DOI: 10.1073/pnas.0505379103

    Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria.
    journal, December 1993

    • Donald, R. G.; Roos, D. S.
    • Proceedings of the National Academy of Sciences, Vol. 90, Issue 24
    • DOI: 10.1073/pnas.90.24.11703

    Jalview Version 2--a multiple sequence alignment editor and analysis workbench
    journal, January 2009


    A Novel Calcium-Dependent Protein Kinase Inhibitor as a Lead Compound for Treating Cryptosporidiosis
    journal, July 2013

    • Castellanos-Gonzalez, Alejandro; White, A. Clinton; Ojo, Kayode K.
    • The Journal of Infectious Diseases, Vol. 208, Issue 8
    • DOI: 10.1093/infdis/jit327

    Novel insights into the regulation of malarial calcium-dependent protein kinase 1
    journal, August 2012

    • Ahmed, Anwar; Gaadhe, Kavita; Sharma, Guru Prasad
    • The FASEB Journal, Vol. 26, Issue 8
    • DOI: 10.1096/fj.12-203877

    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

    Structure of the CaMKIIδ/Calmodulin Complex Reveals the Molecular Mechanism of CaMKII Kinase Activation
    journal, July 2010


    A Forward Genetic Screen Reveals that Calcium-dependent Protein Kinase 3 Regulates Egress in Toxoplasma
    journal, November 2012


    TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells
    journal, December 2012