What is it about?
The three-dimensional structure of indole-3-glycerol phos- phate synthase (IGPS) from the thermophilic bacterium Thermus thermophilus HB8 (TtIGPS) has been determined at 1.8 A ̊ resolution. The structure adopts a typical (/)8- barrel fold with an additional N-terminal extension of 46 residues. A detailed comparison of the crystal structure of TtIGPS with available structures of IGPS from the archaeon Sulfolobus solfataricus (SsIGPS) and the bacteria Thermotoga maritima (TmIGPS) and Escherichia coli (EcIGPS) has been performed. Although the overall folds of the proteins are the same, there are differences in amino-acid composition, structural rigidity, ionic features and stability clusters which may account for the high thermostability of the hyperthermo- philic (SsIGPS and TmIGPS) and thermophilic (TtIGPS) proteins when compared with the mesophilic EcIGPS. The thermostability of IGPS seems to be established mainly by favourable interactions of charged residues, salt bridges and the spatial distribution of relatively rigid clusters of exten- sively interacting residues.
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Why is it important?
To gain a more general insight into IGPS adaptation over a wide range of tempera- tures, the single-domain structural model of a moderately thermophilic TtIGPS having To = 345 K was compared with the crystal structures of EcIGPS (To = 310 K), TmIGPS (To = 356 K) and SsIGPS (To = 363 K). As 10% of all known enzymes contain b/a8 domains (Farber, 1993), understanding the evolution of stability in IGPS may have widespread application.
Perspectives
The present cluster description provides a potential effective strategy for converting a starting three-dimensional structure of a mesophilic protein into a thermophilic one. The approach relies on estimation of the SC clusters of the source and target proteins based on the van der Waals radii of residue atoms and replacement by a suitable conformer of a residue that enhances and/or improves local interactions to create extra SC clusters. Since mutations are made only to residues that are on or very close to the surface of the protein, it is highly unlikely that they will affect the three-dimensional architecture of the protein. Thus, proteins designed following an outer SC-cluster strategy are expected to fold and also to function properly. Although the data set considered in this study was limited to four IGPS proteins, the reliable observation of extra outer SC-cluster residues in thermophilic proteins is significant. Since (/)8-barrel structures have high structural similarity, we believe that the extra outer SC clusters would work to increase thermal stability in general. The tendency of a protein to expand outer SC segments may be a natural step-by-step approach to adapt itself to higher temperatures. The identified features of SC clusters and salt bridges which make IGPS more adaptable to high temperature should be helpful for future biotechnological applications and provide a useful guide for site-directed mutagenesis aimed at improving the thermostability of (/)8-barrel proteins.
Dr Bagautdin Bagautdinov
Read the Original
This page is a summary of: Structure of indole-3-glycerol phosphate synthase fromThermus thermophilusHB8: implications for thermal stability, Acta Crystallographica Section D Biological Crystallography, November 2011, International Union of Crystallography,
DOI: 10.1107/s0907444911045264.
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