Modeling the biochemical differences between rabbit muscle and human liver phosphorylase

V. L. Rath, C. B. Newgard, S. R. Sprang, E. J. Goldsmith, J. Fletterick

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Glycogen phosphorylases catalzye the regulated breakdown of glycogen to glucose‐1‐phosphate. In mammals, glycogen phosphorylase occurs in three different isozymes called liver, muscle and brain after the tissues in which they are prefer entially expressed. The muscle isozyme binds and is activated cooperatively by AMP. In contrast, the liver enzyme binds AMP noncooperatively and is poorly activated. The amino acid sequence of human liver phosphorylase is 80% identical with rabbit muscle phosphorylase, and those residues which contact AMP are conserved. Using computer graphics software, we replaced side chains of the known rabbit muscle structure with those of human liver phosphorylase and interpreted the effects of these changes in order to account for the biochemical differences between them. We have identified two substitutions in liver phosphorylase potentially important in altering the cooperative binding and activation of this isozyme by AMP.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalProteins: Structure, Function, and Bioinformatics
Volume2
Issue number3
DOIs
StatePublished - 1987

Keywords

  • AMP
  • allosteric
  • protein structure
  • tissue‐specific isozymes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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