Adjustment of conformational flexibility is a key event in the thermal adaptation of proteins. Academic Article uri icon

Overview

abstract

  • 3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic Escherichia coli, but has an approximately 17 degreesC higher melting temperature. Its temperature optimum is 22-25 degreesC higher than that of the E. coli enzyme; however, it is hardly active at room temperature. The increased conformational rigidity required to stabilize the thermophilic enzyme against heat denaturation might explain its different temperature-activity profile. Hydrogen/deuterium exchange studies were performed on this thermophilic-mesophilic enzyme pair to compare their conformational flexibilities. It was found that Th. thermophilus IPMDH is significantly more rigid at room temperature than E. coli IPMDH, whereas the enzymes have nearly identical flexibilities under their respective optimal working conditions, suggesting that evolutionary adaptation tends to maintain a "corresponding state" regarding conformational flexibility. These observations confirm that conformational fluctuations necessary for catalytic function are restricted at room temperature in the thermophilic enzyme, suggesting a close relationship between conformational flexibility and enzyme function.

publication date

  • June 23, 1998

Research

keywords

  • Alcohol Oxidoreductases
  • Protein Folding

Identity

PubMed Central ID

  • PMC22632

Scopus Document Identifier

  • 0032560505

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.13.7406

PubMed ID

  • 9636162

Additional Document Info

volume

  • 95

issue

  • 13