Accurate Prediction of Amide Exchange in the Fast Limit Reveals Thrombin Allostery.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
08 01 2019
08 01 2019
Historique:
received:
20
08
2018
revised:
02
11
2018
accepted:
19
11
2018
pubmed:
19
12
2018
medline:
3
1
2020
entrez:
19
12
2018
Statut:
ppublish
Résumé
Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) of proteins has become extremely popular for identifying ligand-binding sites, protein-protein interactions, intrinsic disorder, and allosteric changes upon protein modification. Such phenomena are revealed when amide exchange is measured in the fast limit, that is, within a few minutes of exchange in deuterated buffer. The HDXMS data have a resolution of the length of peptides and are difficult to interpret because many different phenomena lead to changes in hydrogen/deuterium exchange. We present a quantitative analysis of accelerated molecular dynamics simulations that provides impressive agreement with peptide-length HDXMS data. Comparative analysis of thrombin and a single-point mutant reveals that the simulation analysis can distinguish the subtle differences in exchange due to mutation. In addition, the results provide a deeper understanding of the underlying changes in dynamics revealed by the HDXMS that extend far from the site of mutation.
Identifiants
pubmed: 30558884
pii: S0006-3495(18)31288-8
doi: 10.1016/j.bpj.2018.11.023
pmc: PMC6342732
pii:
doi:
Substances chimiques
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-56Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL127041
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008326
Pays : United States
Informations de copyright
Copyright © 2018. Published by Elsevier Inc.
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