6ICD

REGULATION OF AN ENZYME BY PHOSPHORYLATION AT THE ACTIVE SITE

Summary for 6ICD

• Entry DOI: 10.2210/pdb6icd/pdb
• Descriptor: ISOCITRATE DEHYDROGENASE (2 entities in total)
• Functional Keywords: oxidoreductase (nad(a)-choh(d))
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 45837.57

Authors

Hurley, J.H.,Dean, A.M.,Sohl, J.L.,Koshlandjunior, D.E.,Stroud, R.M. (deposition date: 1990-05-30, release date: 1991-10-15, Last modification date: 2024-03-13)

Primary citation

Hurley, J.H.,Dean, A.M.,Sohl, J.L.,Koshland, D.E.,Stroud, R.M.
Regulation of an enzyme by phosphorylation at the active site.
Science, 249:1012-1016, 1990

PubMed Abstract: 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.

PubMed: 2204109

Experimental method

X-RAY DIFFRACTION (2.8 Å)