title: 2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: possible determinants of protein stability.
abstract: BACKGROUND
  Recent efforts to understand the basis of protein stability have focused attention on comparative studies of proteins from hyperthermophilic and mesophilic organisms. Most work to date has been on either oligomeric enzymes or monomers comprising more than one domain. Such studies are hampered by the need to distinguish between stabilizing interactions acting between subunits or domains from those acting within domains. In order to simplify the search for determinants of protein stability we have chosen to study the monomeric enzyme indole-3-glycerol phosphate synthase from the hyperthermophilic archaeon Sulfolobus solfataricus (sIGPS), which grows optimally at 90 degrees C.
  
  
  RESULTS
  The 2.0 A crystal structure of sIGPS was determined and compared with the known 2.0 A structure of the IGPS domain of the bifunctional enzyme from the mesophilic bacterium Escherichia coli (eIGPS). sIGPS and eIGPS have only 30% sequence identity, but share high structural similarity. Both are single-domain (beta/alpha)8 barrel proteins, with one (eIGPS) or two (sIGPS) additional helices inserted before the first beta strand. The thermostable sIGPS has many more salt bridges than eIGPS. Several salt bridges crosslink adjacent alpha helices or participate in triple or quadruple salt-bridge clusters. The number of helix capping, dipole stabilizing and hydrophobic interactions is also increased in sIGPS.
  
  
  CONCLUSIONS
  The higher stability of sIGPS compared with eIGPS seems to be the result of several improved interactions. These include a larger number of salt bridges, stabilization of alpha helices and strengthening of both polypeptide chain termini and solvent-exposed loops.
authors: Department of Structural Biology, University of Basel, Switzerland.
authors: M
authors: M
authors: Hennig
authors: B
authors: B
authors: Darimont
authors: R
authors: R
authors: Sterner
authors: K
authors: K
authors: Kirschner
authors: J N
authors: JN
authors: Jansonius
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D007209:Indole-3-Glycerol-Phosphate Synthase / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016944:Sulfolobus / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010710:Phosphates; D011993:Recombinant Fusion Proteins; D001120:Arginine; D000445:Aldehyde Oxidoreductases; C080010:aldehyde ferredoxin oxidoreductase; D007209:Indole-3-Glycerol-Phosphate Synthase