Protein Name

3-isopropylmalate dehydrogenase


Thermus thermophilus (bacteria,thermophile)

Biological Context

Thermophilic organisms or thermophiles live in high temperature environment, and are a class of extremophilic organisms that live in extreme (hot, acidic, salty, etc.) environments not suitable for normal prokaryotic or eukaryotic organisms. It is known that for instance high temperatures tend to denature proteins and a body temperature in excess of 38 degrees centigrade means serious problems for humans. Thermophiles, however, can live in boiling water and still have functioning metabolisms. Thermus thermophilus, the organism from which the protein here was extracted, is one such example. Although many thermophiles are archaebacteria, Thermus thermophilus is an eubacterium, just as Escherichia coli or Bacillus subtilis. It is therefore interesting to study proteins from such organism to see what makes it possible for them to exist in extreme environments.

Structure Description


The protein here is an enzyme converting one chemical compound, isopropylmalate, into another, ketoisocaproate. This reaction is a step of the leucine biosynthesis, and this enzyme acts with the help of a cofactor Nicotineamide-adenine dinucleotide (NAD) which receives an electron to be reduced to NADH. This is a fairly common process and other structures employing NAD have been studied well. So what makes it possible for Thermus thermophilus to live in such a hot environment? Its chemical composition, the amino acid sequence, is not so different from similar proteins from other organisms. Careful comparison seems to indicate that a single change of an amino acid, from a hydrophilic glutamine to a hydrophobic leucine, may be the main reason. The inside of proteins usually tends to be hydrophobic and the outside hydrophilic (except for membrane proteins) because they exist in aqueous environments. Therefore, having a glutamine in a hydrophobic environment makes the protein more unstable. This is one of the earlier studies on such an extremophile organism and maybe more studies now underway may help to shed more light on this problem.

Protein Data Bank (PDB)



  • Imada, K. Sato, M. Tanaka, N. Katsube, Y. Matsuura, Y. Oshima, T.; "Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution."; J. Mol. Biol.; (1991) 222:725-738 PubMed:1748999.


author: Arno Paehler; revised by Akira Kinjo

Japanese version:PDB:1IPD