Modeling the biochemical differences between rabbit muscle and human liver phosphorylase.

Published

Journal Article

Glycogen phosphorylases catalyze 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 preferentially 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.

Full Text

Duke Authors

Cited Authors

  • Rath, VL; Newgard, CB; Sprang, SR; Goldsmith, EJ; Fletterick, RJ

Published Date

  • 1987

Published In

Volume / Issue

  • 2 / 3

Start / End Page

  • 225 - 235

PubMed ID

  • 3447179

Pubmed Central ID

  • 3447179

International Standard Serial Number (ISSN)

  • 0887-3585

Digital Object Identifier (DOI)

  • 10.1002/prot.340020307

Language

  • eng

Conference Location

  • United States