REGULATION OF AN ENZYME BY PHOSPHORYLATION AT THE ACTIVE-SITE

被引:245
|
作者
HURLEY, JH
DEAN, AM
SOHL, JL
KOSHLAND, DE
STROUD, RM
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,GRAD GRP BIOPHYS,SAN FRANCISCO,CA 94143
[3] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720
关键词
D O I
10.1126/science.2204109
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
The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosphorylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.
引用
收藏
页码:1012 / 1016
页数:5
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