Structural, Thermodynamic, and Functional Mechanisms of Adaptations WrbA and AdoMetDC Proteins in Extremophilic Organisms

Abstract

One of the open questions of structural biology is the understanding of the mechanisms %by which enzymes adapt to extreme temperatures, both high (thermophilic) and low (psychrophilic). A model protein used in this study, S-adenosyl-methionine decarboxylase (AdoMetDC), is a key enzyme in the polyamine biosynthesis and thus its activity should be strongly dependent on the environmental variables such as temperature. To date we completed the experimental characterization of the thermophilic AdoMtDC from Termatoga maritima. The processing of TmAdoMetDC that leads to catalytically active enzyme is undetectable at room temperature, but increases with the increase in temperature (k=0.41+/-0.08 h(exp -1)(exp -1) at 65C). The binding constant for MMTA, an inhibitor that mimics natural substrate S adenosyl-methionine, was found to be on the order of 1 micron. A paper that summarizes these results is currently in preparation. The genes for AdoMtDC from five different bacteria have been cloned: Leptospira interrogans (psychiophile), Exiguobacterium sibiricum, (psychrophile), Petrotoga mobilis (thermophilic anaerobe), and Oceanobacillus iheyensis (halophilic). All these proteins have been expressed and purified, and structural (crystallization for x-ray analysis), biophysical (e.g. stability, oligomerization) and biochemical (activity profile as a function of temperature and salt concentrations, activation energy) experiments are currently in progress.

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Document Details

Document Type
Technical Report
Publication Date
Aug 15, 2007
Accession Number
ADA478746

Entities

People

  • George Makhatadze

Organizations

  • Penn State College of Medicine

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Amines
  • Amino Acids
  • Anabolism
  • Bacteria
  • Boltzmann Equation
  • Chemical Reaction Properties
  • Climate Change
  • Crystal Structure
  • Crystallization
  • Dissociation
  • Energy
  • Experimental Data
  • Heat Of Activation
  • Methionine
  • Spectra
  • Substrates
  • X Rays

Fields of Study

  • Biology

Readers

  • Materials Science and Engineering.
  • Microbial Pathology
  • Molecular and Cellular Biochemistry

Technology Areas

  • Biotechnology