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
Toyokazu Ishida

Abstract

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 Asp102 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 (1)H chemical shift of H(epsilon)(1) and H(delta)(1) in His57. The (15)N and (13)C 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 origi...Continue Reading

References

Aug 5, 1994·Journal of Molecular Biology·Z S DerewendaP M Kobos
Sep 25, 1998·The Journal of Biological Chemistry·W W ClelandJ A Gerlt
Mar 27, 2002·Journal of Computational Chemistry·Martin J Field
Apr 25, 2002·Annual Review of Physical Chemistry·Eric Oldfield
Jul 10, 2003·Journal of the American Chemical Society·James L SudmeierWilliam W Bachovchin
Aug 21, 2003·Journal of the American Chemical Society·G Andrés CisnerosWeitao Yang
Jun 4, 2004·Journal of the American Chemical Society·Toyokazu Ishida, Shigeki Kato

❮ Previous
Next ❯

Citations

Apr 16, 2013·Physical Chemistry Chemical Physics : PCCP·Hwee-Jia Tan, Ryan P A Bettens
Nov 29, 2013·Journal of the Royal Society, Interface·Hiroshi Ishikita, Keisuke Saito
May 12, 2007·Journal of Molecular Graphics & Modelling·Marc W van der KampAdrian J Mulholland
Apr 18, 2009·Magnetic Resonance in Chemistry : MRC·Marcelo A Muñoz, Pedro Joseph-Nathan
Jan 29, 2009·Angewandte Chemie·Hans Martin Senn, Walter Thiel
Nov 14, 2018·The Journal of General Physiology·Kristen A Gaffney, Heedeok Hong
Oct 16, 2016·The Journal of Biological Chemistry·Elizabeth C WittenbornCatherine L Drennan
Jul 25, 2020·Chembiochem : a European Journal of Chemical Biology·Prashasti KumarMatthew J Cuneo
Apr 4, 2021·International Journal of Molecular Sciences·Brigitta Elsässer, Peter Goettig
May 9, 2008·The Journal of Physical Chemistry. B·Steve Scheiner
Nov 6, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·M Trent KempYu Chen
Apr 28, 2007·Journal of the American Chemical Society·Yuhui ChengJ Andrew McCammon
Jan 31, 2008·Accounts of Chemical Research·Ronald J T HoukEric V Anslyn
Apr 7, 2015·Chemical Reviews·Michael A Collins, Ryan P A Bettens
Jun 10, 2015·Journal of the American Chemical Society·Derek A NicholsYu Chen
Apr 6, 2013·Biochemistry·Marc W van der Kamp, Adrian J Mulholland

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.