8icd
REGULATION OF AN ENZYME BY PHOSPHORYLATION AT THE ACTIVE SITE
OverviewOverview
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 phosporylation 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.
About this StructureAbout this Structure
8ICD is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
Regulation of an enzyme by phosphorylation at the active site., Hurley JH, Dean AM, Sohl JL, Koshland DE Jr, Stroud RM, Science. 1990 Aug 31;249(4972):1012-6. PMID:2204109 Page seeded by OCA on Sun May 4 22:49:48 2008