The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate

Structure
M S JuricaB L Stoddard

Abstract

Yeast pyruvate kinase (PK) catalyzes the final step in glycolysis. The enzyme therefore represents an important control point and is allosterically activated by fructose-1,6-bisphosphate (FBP). In mammals the enzyme is found as four different isozymes with different regulatory properties: two of these isozymes are produced by alternate splicing. The allosteric regulation of PK is directly related to proliferation of certain cell types, as demonstrated by the expression of an allosterically regulated isozyme in tumor cells. A model for the allosteric transition from the inactive (T) state to the active (R) state has been proposed previously, but until now the FBP-binding site had not been identified. We report here the structures of PK from yeast complexed with a substrate analog and catalytic metal ions in the presence and absence of bound FBP. The allosteric site is located 40 A from the active site and is entirely located in the enzyme regulatory (C) domain. A phosphate-binding site for the allosteric activator is created by residues encoded by a region of the gene corresponding to the alternately spliced exon of mammalian isozymes. FBP activation appears to induce several conformational changes among active-site sidechains t...Continue Reading

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Related Concepts

Nested Transcripts
Manganese
Potassium
Protein Conformation
Glycolate Ethers
Phosphoglycolic acid
R-Type Pyruvate Kinase
Cistron
fructose-1,6-diphosphate, calcium (1: 2) salt
Saccharomyces cerevisiae

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