scholarly journals Correction to “Fluoroketone Inhibition of Ca2+-Independent Phospholipase A2 through Binding Pocket Association Defined by Hydrogen/Deuterium Exchange and Molecular Dynamics”

2013 ◽  
Vol 135 (15) ◽  
pp. 5932-5932 ◽  
Author(s):  
Yuan-Hao Hsu ◽  
Denis Bucher ◽  
Jian Cao ◽  
Sheng Li ◽  
Sheng-Wei Yang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Phospholipase A2 ◽  
Binding Pocket ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium

scholarly journals Conservation of the conformational dynamics and ligand binding within M49 enzyme family

RSC Advances ◽  
2018 ◽  
Vol 8 (24) ◽  
pp. 13310-13322 ◽  
Author(s):  
Saša Kazazić ◽  
Zrinka Karačić ◽  
Igor Sabljić ◽  
Dejan Agić ◽  
Marko Tomin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Dynamics ◽  
Ligand Binding ◽  
Conformational Dynamics ◽  
Md Simulations ◽  
Dipeptidyl Peptidase ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Enzyme Family ◽  
Hydrogen Deuterium

The hydrogen deuterium exchange (HDX) mass spectrometry combined with molecular dynamics (MD) simulations was employed to investigate conformational dynamics and ligand binding within the M49 family (dipeptidyl peptidase III family).

Hydrogen/Deuterium Exchange and Molecular Dynamics Analysis of Amyloid Fibrils Formed by a D69K Charge-Pair Mutant of Human Apolipoprotein C-II

Biochemistry ◽  
2015 ◽  
Vol 54 (31) ◽  
pp. 4805-4814 ◽  
Author(s):  
Yu Mao ◽  
Courtney O. Zlatic ◽  
Michael D. W. Griffin ◽  
Geoffrey J. Howlett ◽  
Nevena Todorova ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amyloid Fibrils ◽  
Deuterium Exchange ◽  
Dynamics Analysis ◽  
Hydrogen Deuterium Exchange ◽  
Human Apolipoprotein ◽  
Apolipoprotein C ◽  
Hydrogen Deuterium

scholarly journals Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange

2011 ◽  
Vol 25 (1) ◽  
pp. 15-31 ◽  
Author(s):  
A. C. M. Figueira ◽  
D. M. Saidemberg ◽  
P. C. T. Souza ◽  
L. Martínez ◽  
T. S. Scanlan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Ligand Binding ◽  
Conformational Changes ◽  
Thyroid Hormone Receptor ◽  
Binding Pocket ◽  
Deuterium Exchange ◽  
Site Directed Mutagenesis ◽  
Hydrogen Deuterium Exchange ◽  
Ligand Binding Pocket ◽  
Hydrogen Deuterium

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T3) or antagonist (NH3). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10–H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, C-terminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T3, but not NH3, increases accessibility of the upper part of H3–H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T3 but not NH3. We present data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes.

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