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Absolute and Local Extreme Values01:22

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The highest and lowest values of a function, relative to a reference axis, are known as extreme values. These include absolute maximum and absolute minimum values, which represent the highest and lowest points the function reaches across its entire domain. Within a restricted portion of the function, the highest and lowest values are referred to as local maximum and local minimum values, respectively.Periodic functions, such as sine and cosine, show extreme values at infinitely many points due...
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Extreme biophysics: Enzymes under pressure.

Qi Huang1, Jocelyn M Rodgers1,2, Russell J Hemley3

  • 1Department of Chemistry, Georgetown University, Washington, DC, 20057.

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Piezophilic microbes utilize unique molecular adaptations for high-pressure environments. This study reveals how dihydrofolate reductase flexibility in Moritella profunda enhances activity under pressure, aiding deep-sea life.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Extremophile Microbiology
  • Computational Biology

Background:

  • Piezophilic (pressure-loving) organisms thrive in high-pressure deep-sea environments.
  • Understanding how their biomolecules, such as enzymes, maintain function under extreme pressure is crucial.
  • Dihydrofolate reductase (DHFR) is essential for cellular metabolism in all organisms.

Purpose of the Study:

  • To investigate the molecular factors contributing to the enhanced activity of DHFR from the piezophilic Moritella profunda under high pressure.
  • To compare the pressure-dependent flexibility of M. profunda DHFR with that of DHFR from the mesophilic Escherichia coli.

Main Methods:

  • Utilized molecular dynamics simulations at various temperatures and pressures.
  • Analyzed enzyme flexibility and stability in response to hydrostatic pressure.
  • Focused on collective motions occurring on the 10-nanosecond timescale.

Main Results:

  • Identified collective motions on the 10-ns timescale as critical for DHFR flexibility and activity at the growth conditions of M. profunda.
  • Demonstrated that high pressure may enhance the adaptation of deep-sea enzymes to low temperatures.
  • Observed differences in flexibility and stability between M. profunda DHFR and E. coli DHFR under varying pressures.

Conclusions:

  • Enzyme flexibility, particularly collective motions, is key for piezophilic adaptation.
  • High pressure can play a role in optimizing enzyme function at low temperatures for deep-sea organisms.
  • The findings provide insights into the molecular mechanisms enabling life in extreme marine environments.