TY - JOUR
T1 - Modeling the biochemical differences between rabbit muscle and human liver phosphorylase
AU - Rath, Virginia L.
AU - Newgard, Christopher B.
AU - Sprang, Stephen R.
AU - Goldsmith, Elizabeth J.
AU - Fletterick, Robert J.
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
KW - AMP
KW - allosteric
KW - protein structure
KW - tissue‐specific isozymes
UR - http://www.scopus.com/inward/record.url?scp=0023613819&partnerID=8YFLogxK
U2 - 10.1002/prot.340020307
DO - 10.1002/prot.340020307
M3 - Article
C2 - 3447179
AN - SCOPUS:0023613819
SN - 0887-3585
VL - 2
SP - 225
EP - 235
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
IS - 3
ER -