TY - JOUR
T1 - Isothermal titration calorimetry of membrane proteins - Progress and challenges
AU - Rajarathnam, Krishna
AU - Rösgen, Jörg
N1 - Funding Information:
This work was supported in part by grants P01HL107152 1 and R21AI09797 5 to K.R. and R01GM049760 to J.R. from the National Institutes of Health . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank the lab members for their critical reading of the manuscript.
PY - 2014
Y1 - 2014
N2 - Integral membrane proteins, including G protein-coupled receptors (GPCR) and ion channels, mediate diverse biological functions that are crucial to all aspects of life. The knowledge of the molecular mechanisms, and in particular, the thermodynamic basis of the binding interactions of the extracellular ligands and intracellular effector proteins is essential to understand the workings of these remarkable nanomachines. In this review, we describe how isothermal titration calorimetry (ITC) can be effectively used to gain valuable insights into the thermodynamic signatures (enthalpy, entropy, affinity, and stoichiometry), which would be most useful for drug discovery studies, considering that more than 30% of the current drugs target membrane proteins. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.
AB - Integral membrane proteins, including G protein-coupled receptors (GPCR) and ion channels, mediate diverse biological functions that are crucial to all aspects of life. The knowledge of the molecular mechanisms, and in particular, the thermodynamic basis of the binding interactions of the extracellular ligands and intracellular effector proteins is essential to understand the workings of these remarkable nanomachines. In this review, we describe how isothermal titration calorimetry (ITC) can be effectively used to gain valuable insights into the thermodynamic signatures (enthalpy, entropy, affinity, and stoichiometry), which would be most useful for drug discovery studies, considering that more than 30% of the current drugs target membrane proteins. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.
KW - Affinity
KW - Drug discovery
KW - Enthalpy
KW - Isothermal titration calorimetry (ITC)
KW - Membrane proteins
KW - Thermodynamics
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U2 - 10.1016/j.bbamem.2013.05.023
DO - 10.1016/j.bbamem.2013.05.023
M3 - Review article
C2 - 23747362
AN - SCOPUS:84888318270
SN - 0005-2736
VL - 1838
SP - 69
EP - 77
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 1 PARTA
ER -