pKaShift Effects on Backbone Amide Base-Catalyzed Hydrogen Exchange Rates in Peptides

1998 ◽  
Vol 120 (15) ◽  
pp. 3735-3738 ◽  
Author(s):  
Federico Fogolari ◽  
Gennaro Esposito ◽  
Paolo Viglino ◽  
James M. Briggs ◽  
J. Andrew McCammon
Keyword(s):  
Exchange Rates ◽  
Hydrogen Exchange ◽  
Backbone Amide

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.

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

15N Isotopic Labeling and Amide Hydrogen Exchange Rates of Oxidized Iso-1-cytochromec

1997 ◽  
Vol 119 (41) ◽  
pp. 9899-9900 ◽  
Author(s):  
Susan M. Baxter ◽  
Terry L. Boose ◽  
Jacquelyn S. Fetrow
Keyword(s):  
Exchange Rates ◽  
Hydrogen Exchange ◽  
Isotopic Labeling ◽  
Amide Hydrogen ◽  
Amide Hydrogen Exchange
Sign in / Sign up

Export Citation Format

Share Document