Adjustment of conformational flexibility is a key event in the thermal adaptation of proteins

被引:489
作者
Závodszky, P
Kardos, J
Svingor, A
Petsko, GA
机构
[1] Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1518 Budapest, Hungary
[2] Eotvos Lorand Univ, Dept Biochem, H-1088 Budapest, Hungary
[3] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA
关键词
D O I
10.1073/pnas.95.13.7406
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic Escherichia coli, but has an approximately 17 degrees C higher melting temperature. Its temperature optimum is 22-25 degrees C higher than that of the E. coli enzyme; however, it is hardly active at room temperature. The increased conformational rigidity required to stabilize the thermophilic enzyme against heat denaturation might explain its different temperature-activity profile. Hydrogen/deuterium exchange studies were performed on this thermophilic-mesophilic enzyme pair to compare their conformational flexibilities. It was found that Th. thermophilus IPMDH is significantly more rigid at room temperature than E. coli IPMDH, whereas the enzymes have nearly identical flexibilities under their respective optimal working conditions, suggesting that evolutionary adaptation tends to maintain a "corresponding state" regarding conformational flexibility. These observations confirm that conformational fluctuations necessary for catalytic function are restricted at room temperature in the thermophilic enzyme, suggesting a close relationship between conformational flexibility and enzyme function.
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页码:7406 / 7411
页数:6
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