[ccp4bb]: Thermostability vs Structure

[Rudolf Ladenstein <Rudolf.Ladenstein@csb.ki.se>]

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Dear Francisco,

There is, I am afraid to say, quite some consensus on protein
thermostability, especially for proteins from hyperthermophiles, which
usually grow at temperatures near to or above 100 deg Celsius (it would be
interesting to know from which organism your thermostable oxidase is
obtained and to which mesophile you have compared your structure!)

>From statistical analysis of large structure data bases, genomic analysis
and structural comparisons it is obvious, that in hyperthermostable
structures at least two contributions to the free energy of stabilization
are optimized: these are 1.) the electrostatic term (taking into account
repulsive and attractive electrostatic interactions, e.g. salt bridge
interactions, dipole-dipole interactions... and 2.) the hydrophobic term,
which means that the hydrophobic accessible surface in proteins from
hyperthermophiles is generally reduced, because interactions of water with
hydrophobic groups are energetically unfavourable. However, these  features
can be expressed to different extents in different proteins, these are
statistical findings... and each protein probably has developed its own and
characteristic stabilization strategy

Those effects can also be seen, but much less clearly, in proteins from
thermophiles, which usually grow around 60 - 80 deg Celsius. 

A very clear example was found in icosahedral Lumazine synthase from
Aquifex aeolicus, compared to its mesophilic counterpart from Bacillus
subtilis (X. Zhang et al(2001) J Mol Biol 306, 1099-1114.

If you wish to learn more about the energetic optimization of protein
structures and thermostability, I can recommend the following papers:

V. Spassov et al (1995) Protein Science 4, 1516-1527
A Karshikoff & R Ladenstein (2001) TIBS Vol 26 Nr 9, 550-556

with kind regards,

Rudolf Ladenstein
Professor of Structural Biochemistry
Karolinska Institutet NOVUM
Dept. of Biosciences
S-14157 Huddinge, Sweden