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 Citations (Scopus)

Abstract

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.

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

Fingerprint

Phosphorylases
Liver
Muscle
Adenosine Monophosphate
Rabbits
Muscles
Isoenzymes
Glycogen Phosphorylase
Computer Graphics
Mammals
Computer graphics
Glycogen
Amino Acid Sequence
Brain
Substitution reactions
Software
Chemical activation
Tissue
Amino Acids
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology

Cite this

Modeling the biochemical differences between rabbit muscle and human liver phosphorylase. / Rath, V. L.; Newgard, C. B.; Sprang, S. R.; Goldsmith, E. J.; Fletterick, J.

In: Proteins: Structure, Function and Genetics, Vol. 2, No. 3, 1987, p. 225-235.

Research output: Contribution to journalArticle

Rath, V. L. ; Newgard, C. B. ; Sprang, S. R. ; Goldsmith, E. J. ; Fletterick, J. / Modeling the biochemical differences between rabbit muscle and human liver phosphorylase. In: Proteins: Structure, Function and Genetics. 1987 ; Vol. 2, No. 3. pp. 225-235.
@article{5ab7169379cb4aa5903b1f7edacdbb1b,
title = "Modeling the biochemical differences between rabbit muscle and human liver phosphorylase",
abstract = "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.",
author = "Rath, {V. L.} and Newgard, {C. B.} and Sprang, {S. R.} and Goldsmith, {E. J.} and J. Fletterick",
year = "1987",
language = "English (US)",
volume = "2",
pages = "225--235",
journal = "Proteins: Structure, Function and Bioinformatics",
issn = "0887-3585",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Modeling the biochemical differences between rabbit muscle and human liver phosphorylase

AU - Rath, V. L.

AU - Newgard, C. B.

AU - Sprang, S. R.

AU - Goldsmith, E. J.

AU - Fletterick, J.

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0023613819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023613819&partnerID=8YFLogxK

M3 - Article

C2 - 3447179

AN - SCOPUS:0023613819

VL - 2

SP - 225

EP - 235

JO - Proteins: Structure, Function and Bioinformatics

JF - Proteins: Structure, Function and Bioinformatics

SN - 0887-3585

IS - 3

ER -