MISC

2006年5月

Low-barrier hydrogen bond hypothesis in the catalytic triad residue of serine proteases: Correlation between structural rearrangement and chemical shifts in the acylation process

BIOCHEMISTRY
  • T Ishida

45
17
開始ページ
5413
終了ページ
5420
記述言語
英語
掲載種別
DOI
10.1021/bi051515b
出版者・発行元
AMER CHEMICAL SOC

To elucidate the catalytic advantage of the low-barrier hydrogen bond (LBHB), we analyze the hydrogen bonding network of the catalytic triad (His57-Asp102-Ser195) of serine protease trypsin, one of the best examples of the LBHB reaction mechanism. Especially, we focus on the correlation between the change of the chemical shifts and the structural rearrangement of the active site in the acylation process. To clarify LBHB, we evaluate the two complementary properties. First, we calculate the NMR chemical shifts of the imidazole ring of His57 by the gauge-including atomic orbital (GIAO) approach within the ab initio QM/MM framework. Second, the free energy profile of the proton transfer from His57 to Asp 102 in the tetrahedral intermediate is obtained by ab initio QM/MM calculations combined with molecular dynamics free energy perturbation (MD-FEP) simulations. The present analyses reveal that the calculated shifts reasonably reproduce the observed values for H-1 chemical shift of H-epsilon 1 and H-delta 1 in His57. The N-15 and C-13 chemical shifts are also consistent with the experiments. It is also shown that the proton between His57 and Asp102 is localized at the His57 side. This largely downfield chemical shift is originated from the strong electrostatic interaction, not a covalent-like bonding character between His57 and Asp102. Also, it is proved that a slight downfield character of H-epsilon 1 is originated from a electrostatic interaction between His57 and the backbone carbonyl group of Val213 and Ser214. These downfield chemical shifts are observed only when the tetrahedral intermediate is formed in the acylation process.

Web of Science ® 被引用回数 : 55

リンク情報
DOI
https://doi.org/10.1021/bi051515b
CiNii Articles
http://ci.nii.ac.jp/naid/80019158559
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/16634622
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000237225500003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1021/bi051515b
  • ISSN : 0006-2960
  • CiNii Articles ID : 80019158559
  • PubMed ID : 16634622
  • Web of Science ID : WOS:000237225500003

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