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Related Concept Videos

Conformity01:20

Conformity

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Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Conformations of Butane02:20

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Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
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Conformations of Cycloalkanes02:29

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Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3  hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
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Conformations of Cyclohexane02:11

Conformations of Cyclohexane

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Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
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Conformations of Ethane and Propane02:18

Conformations of Ethane and Propane

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In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
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Related Experiment Video

Updated: Feb 13, 2026

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
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Interplay between conformational selection and zymogen activation.

Pradipta Chakraborty1, Laura Acquasaliente1, Leslie A Pelc1

  • 1Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA.

Scientific Reports
|March 8, 2018
PubMed
Summary

Zymogen activation involves conformational changes. Prothrombin (thrombin precursor) shifts from an inaccessible to an accessible active site conformation, increasing ligand binding affinity 700-fold during its conversion to thrombin.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Protease research

Background:

  • Trypsin-like proteases function as zymogens, requiring activation for catalytic efficiency.
  • Zymogen activation involves conformational changes that facilitate active site binding and catalysis.
  • Ligand binding studies offer insights into the molecular mechanisms of zymogen activation.

Purpose of the Study:

  • To investigate the conformational changes during the physiological activation of prothrombin to thrombin.
  • To elucidate the role of ligand recognition in understanding zymogen activation.
  • To determine how cleavage events influence the conformational ensemble and binding affinity.

Main Methods:

  • Utilized limited proteolysis to study prothrombin activation.
  • Analyzed ligand binding to the active site in different conformational states (E and E*).
  • Investigated the impact of cleavage at R271 and R320 on enzyme conformation and dynamics.

Main Results:

  • Prothrombin predominantly exists in an inactive E* conformation with an inaccessible active site.
  • Cleavage at R271 shifts the equilibrium towards the active E conformation by removing auxiliary domains.
  • Cleavage at R320 drastically reduces ligand dissociation rates, leading to a 700-fold increase in binding affinity.

Conclusions:

  • Prothrombin activation involves a shift in conformational equilibrium and altered ligand binding dynamics.
  • The findings provide molecular insights into the activation of prothrombin and related zymogens.
  • Understanding these mechanisms is crucial for processes like blood coagulation, complement activation, and fibrinolysis.