Identification of Important Amino Acid Residues of the Na + -Ca 2+ Exchanger Inhibitory Peptide, XIP

1997 ◽  
Vol 156 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Z. He ◽  
N. Petesch ◽  
K.-P. Voges ◽  
W. Röben ◽  
K.D. Philipson
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Inhibitory Peptide ◽  
Important Amino Acid

Important Amino Acid Residues that Confer CYP2C19 Selective Activity to CYP2C9

2008 ◽  
Vol 144 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Y. Wada ◽  
M. Mitsuda ◽  
Y. Ishihara ◽  
M. Watanabe ◽  
M. Iwasaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Important Amino Acid ◽  
Selective Activity

scholarly journals Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease - Inhibitor N3 Complex (PDB ID:6LU7)

2020 ◽  
Author(s):  
Ryo Hatada ◽  
Koji Okuwaki ◽  
Yuji Mochizuki ◽  
Kaori Fukuzawa ◽  
Yuto Komeiji ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Amino Acid ◽  
Molecular Orbital ◽  
Interaction Analysis ◽  
Amino Acid Residues ◽  
Inhibitor Molecule ◽  
Fragment Molecular Orbital ◽  
Important Amino Acid ◽  
Main Protease ◽  
Short Period

The worldwide spread of COVID-19 (new coronavirus found in Wuhan in 2019) is an emergent issue to be tackled. In fact, a great amount of works in various fields have been made in rather short period. Here, we report a fragment molecular orbital (FMO) based interaction analysis on a complex between the SARS-CoV-2 main protease (Mpro) and its peptide-like inhibitor N3 (PDB ID: 6LU7). The target inhibitor molecule was segmented into five fragments in order to capture site specific interactions with amino acid residues of the protease. The interaction energies were decomposed into several contributions, and then the characteristics of hydrogen bonding and dispersion stabilization were made clear. Furthermore, the hydration effect was incorporated by the Poisson-Boltzmann (PB) scheme. From the present FMO study, His41, His163, His164, and Glu166 were found to be the most important amino acid residues of Mpro in interacting with the inhibitor, mainly due to hydrogen bonding. A guideline for optimizations of the inhibitor molecule was suggested as well based on the FMO analysis.

scholarly journals Structural Insights Into the Design of Peptide-based Drug or Diagnostic Reagent Antagonizing SARS-COV-2

2020 ◽  
Author(s):  
junhao jiang ◽  
Ping Deng
Keyword(s):  
Amino Acid ◽  
Binding Affinity ◽  
Great Promise ◽  
Amino Acid Residues ◽  
Important Amino Acid ◽  
Amino Acid Mutations ◽  
Α Helix ◽  
New Interactions ◽  
Structural Insights ◽  
Blocking Capacity

Abstract Background Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2. Methods Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted. Results Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development. Conclusion Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.

Important amino acid residues involved in folding and binding of protein–protein complexes

2017 ◽  
Vol 94 ◽  
pp. 438-444 ◽  
Author(s):  
A. Kulandaisamy ◽  
V. Lathi ◽  
K. ViswaPoorani ◽  
K. Yugandhar ◽  
M.Michael Gromiha
Keyword(s):  
Amino Acid ◽  
Protein Complexes ◽  
Amino Acid Residues ◽  
Important Amino Acid

Abstract 5349: Dual Effects of Nifekalant on I Kr

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mikio Morishima ◽  
Ryoko Niwa ◽  
Takahiro Yamaguchi ◽  
Sara Kato ◽  
Yukiomi Tsuji ◽  
...  
Keyword(s):  
Amino Acid ◽  
Time Constant ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Amino Acid Residues ◽  
Inactivation Curve ◽  
Important Amino Acid ◽  
Agonist Action ◽  
Activation Gate ◽  
Antagonist Action

Purpose: Nifekalant, a potent and common antiarrhythmic drug, has been regarded to treat reentry arrhythmias through I Kr block (antagonist action). But, recently nifekalant was reported to increase I Kr at slight depolarizing level (agonist action) and details are still not known. In this study, profiles and molecular mechanisms of I Kr antagonist and agonist actions by nifekalant were comparatively investigated. Methods: I Kr was measured in rabbit ventricular myocytes. hERG currents were expressed in Xenopus oocytes . An Ala-scanning mutagenesis of hERG channel was performed in S4-S5 linker regions and S6 domain to seek for important amino acid residues to develop agonist action. Results: In I Kr of myocytes, nifekalant (0.3 μM) suppressed currents at all test voltages ranging from −60 mV to +40 mV and showed antagonist action. However, when a preceding depolarizing pulse (+20 mV for 2 sec) was applied, current amplitudes below −20 mV were transiently increased and showed agonist action. When repetitive short depolarizing pulses, mimic action potentials, were applied, agonist action was enhanced at higher frequency. When a preceding depolarizing pulses was prolonged, agonist action rapidly increased (+20 mV, time constant: 428±31 ms, n=4). When an interval at −90 mV between a preceding pulse and a tested depolarization to −50 mV was prolonged, currents were slowly decreased with time constant of 306±55 sec (n=4). These time constants were relatively similar to onset and offset time constant of current blocking by antagonist action (onset at 20 mV: 769±33 ms, offset at −90 mV: 218±44 sec, n=4). Nifekalant shifted activation curve to a hyperpolarizing direction by 28.0±2.5 mV (n=4), but did not affect inactivation curve. In 2 mutations made in the S4–S5 linker, which could affect activation gate, agonist action was abolished but antagonist action was maintained. Conclusions: Our results indicated that both antagonist and agonist actions on I Kr by nifekalant may exhibit continuously within normal range of heart rate, thereby contributing to antiarrhythmic effects. Agonist action may be derived by two factors; first, a binding to amino acid residues same as antagonist action and, second, an interaction with activation gate.

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