pH dependence of individual tryptophan N-1 hydrogen exchange rates in lysozyme and its chemically modified derivatives

Biochemistry ◽  
1987 ◽  
Vol 26 (7) ◽  
pp. 1838-1845 ◽  
Author(s):  
Toshiya Endo ◽  
Tadashi Ueda ◽  
Hidenori Yamada ◽  
Taiji Imoto
Keyword(s):  
Exchange Rates ◽  
Hydrogen Exchange ◽  
Ph Dependence ◽  
Chemically Modified

scholarly journals Hydrogen exchange kinetics of human hemoglobins. The pH dependence of solvent accessibility in cyanomet-, oxy-, and deoxyhemoglobin.

1978 ◽  
Vol 253 (10) ◽  
pp. 3702-3707
Author(s):  
B.E. Hedlund ◽  
P.E. Hallaway ◽  
B.E. Hallaway ◽  
E.S. Benson ◽  
A. Rosenberg
Keyword(s):  
Hydrogen Exchange ◽  
Solvent Accessibility ◽  
Ph Dependence ◽  
Exchange Kinetics ◽  
Kinetics Of

Determination of amide hydrogen exchange rates in peptides by mass spectrometry

1992 ◽  
Vol 64 (20) ◽  
pp. 2456-2458 ◽  
Author(s):  
Geraldine. Thevenon-Emeric ◽  
John. Kozlowski ◽  
Zhongqi. Zhang ◽  
David L. Smith
Keyword(s):  
Mass Spectrometry ◽  
Exchange Rates ◽  
Hydrogen Exchange ◽  
Amide Hydrogen ◽  
Amide Hydrogen Exchange

scholarly journals NMR Hydrogen Exchange and Relaxation Reveal Positions Stabilized by p53 Rescue Mutants N239Y and N235K

2021 ◽  
Author(s):  
Jenaro Soto ◽  
Colleen Moody ◽  
Ali Alhoshani ◽  
Marilyn Sanchez-Bonilla ◽  
Daisy Martinon ◽  
...  
Keyword(s):  
Exchange Rates ◽  
Protein Dynamics ◽  
Protein Sequence ◽  
Hydrogen Exchange ◽  
Cancer Therapeutics ◽  
Drug Efficacy ◽  
Dna Binding Domain ◽  
Protein Sequence Analysis ◽  
Stabilizing Effect ◽  
Folding Dynamics

Inactivation of p53 is found in over 50% of all cancers; p53 disfunction is often caused by a single missense mutation localized in the DNA binding domain (DBD). Rescue mutants N235K and N239Y stabilize and restore function to multiple p53 cancer mutants. Here, we use NMR to compare protein dynamics between WT and rescue mutants to understand the mechanism of stabilization. We measured and compared folding dynamics by calculating protection factors (PFs) from NMR hydrogen exchange rates of backbone amides. We find that both rescue mutants impose a global stabilizing effect that dampens their motions compared to WT DBD, predominantly in the beta-sandwich. However, a few regions become more flexible in rescue mutants. Notably, positions that have increased PFs map to cancer mutants rescued by each mutant. We also compared relaxation results to obtain flexibility information in the ps to ns timescale regime. Protein sequence analysis was used to determine the occurrence of these rescue mutants in nature and showed that 235K is found in mice and rats, but there is no evidence of 239Y occurring naturally in any species. Understanding the mechanism by which stabilizing mutants rescue p53 may reveal novel avenues for the development of cancer therapeutics. Our findings suggest that cancer therapeutics aimed at restoring p53 function could consider protein dynamics as a metric of drug efficacy.

Effect of peptide binding on amide proton exchange rates in the PDZ2 domain from human phosphatase hPTP1E

1998 ◽  
Vol 76 (2-3) ◽  
pp. 334-340 ◽  
Author(s):  
Irena Ekiel ◽  
Denis Banville ◽  
Shi Hsiang Shen ◽  
Kalle Gehring
Keyword(s):  
Exchange Rates ◽  
Ph Dependence ◽  
Guanidine Hydrochloride ◽  
Peptide Binding ◽  
Fluorescence Emission ◽  
Proton Exchange ◽  
Amide Proton ◽  
Amide Proton Exchange ◽  
C Terminus ◽  
Amide Exchange

Amide hydrogen-deuterium exchange rates were measured in the PDZ2 domain from human phosphatase hPTP1E by 1H-15N heteronuclear NMR spectroscopy. Protection factors were calculated for the slowly exchanging hydrogens in both the free PDZ2 domain and its complex with an octapeptide peptide, R-N-E-I-Q-S-L-V, derived from the C-terminus of the Fas receptor. Aside from a short α-helical region α1 (amino acids A-45 to D-49), the pattern of highly protected amides correlated well with the presence of hydrogen bonds in elements of the secondary structure. Hydrogen-bonded amides showed relatively fast exchange rates with half-lives of less than 9 h at pD 7.6 and 8°C. Protection factors, calculated as the ratio of theoretical (denatured) and observed exchange rates, showed less dispersion in maximal values than did the actual exchange rates. This behavior and the large pH dependence of the exchange rates suggest that amide exchange is close to the EX2 limit. In this limit, exchange of the most protected amides occurs through a global unfolding mechanism. The free energy of the unfolding calculated from the largest protection factors is 4.8 ± 0.4 kcal/mol (1 cal = 4.184 J). This ΔG° closely matches the value measured by experiments with guanidine hydrochloride and fluorescence emission spectroscopy. Peptide binding to PDZ2 resulted in mostly global effects and stabilized the folded domain by 1.4 kcal/mol.Key words: PDZ2 from hPTP1E, amide exchange, ligand binding, NMR.

scholarly journals Correction to Empirical Correction for Differences in Chemical Exchange Rates in Hydrogen Exchange-Mass Spectrometry Measurements

2017 ◽  
Vol 89 (24) ◽  
pp. 13673-13673 ◽  
Author(s):  
Ronald T. Toth ◽  
Brittney J. Mills ◽  
Sangeeta B. Joshi ◽  
Reza Esfandiary ◽  
Steven M. Bishop ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Exchange Rates ◽  
Hydrogen Exchange ◽  
Chemical Exchange ◽  
Exchange Mass Spectrometry ◽  
Empirical Correction ◽  
Hydrogen Exchange Mass Spectrometry

scholarly journals Amide proton hydrogen exchange rates for sperm whale myoglobin obtained from 15N-1H NMR spectra

2008 ◽  
Vol 9 (1) ◽  
pp. 186-193 ◽  
Author(s):  
Silvia Cavagnero ◽  
Yves Thériault ◽  
Surinder S. Narula ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Exchange Rates ◽  
1H Nmr ◽  
Nmr Spectra ◽  
Hydrogen Exchange ◽  
Sperm Whale ◽  
1H Nmr Spectra ◽  
Amide Proton ◽  
Sperm Whale Myoglobin
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