2.0 angstrom structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: Possible determinants of protein stability

被引:226
作者
Hennig, M
Darimont, B
Sterner, R
Kirschner, K
Jansonius, JN
机构
[1] UNIV BASEL, BIOZENTRUM, DEPT BIOL STRUCT, CH-4056 BASEL, SWITZERLAND
[2] UNIV BASEL, BIOZENTRUM, DEPT BIOPHYS CHEM, CH-4056 BASEL, SWITZERLAND
关键词
archaea; (beta/alpha)(8) barrel; helix stabilization; salt bridges;
D O I
10.1016/S0969-2126(01)00267-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Recent efforts to understand the basis of protein stability have focussed 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 Angstrom 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 a 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 or helices and strengthening of both polypeptide chain termini and solvent-exposed loops.
引用
收藏
页码:1295 / 1306
页数:12
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