Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Comparative analysis of species-independent, isozyme-specific amino-acid substitutions in mammalian muscle, brain and liver glycogen phosphorylases.

Authors: Hudson, JW  Hefferon, KL  Crerar, MM 
Citation: Hudson JW, etal., Biochim Biophys Acta 1993 Jul 10;1164(2):197-208.
Pubmed: (View Article at PubMed) PMID:7916624

Mammalian glycogen phosphorylases exist as three isozymes, muscle, brain and liver, that exhibit different responses to activation by phosphorylation and AMP, regardless of species. To identify species-independent, amino-acid substitutions that may be important determinants in differential isozyme control, we have sequenced cDNAs containing the entire protein coding regions of rat muscle and brain phosphorylases. Nucleotide sequence comparisons with rat liver, rabbit muscle, and human muscle, brain and liver phosphorylase genes, indicate that muscle and brain isozymes are more related to each other than to the liver isozyme. Unlike the human isozymes, there is little difference in GC content of codons in the rat isozymes. In relation to the rabbit muscle isozyme three-dimensional structure, amino-acid sequence comparisons indicate that very few nonconservative isozyme-specific substitutions occur in buried and dimer contact residues. There is strict conservation of active site, pyridoxal-phosphate-binding site and nucleoside inhibitor site residues, as well as CAP loop and helix-2 residues that comprise the phosphorylation activation and part of the AMP binding sites. In contrast, five liver isozyme-specific substitutions occur between residues 313-325 and another at residue 78 which may be important determinants in the poor activation of this isozyme by AMP. Substitutions in the brain isozyme at residues 21-23, 405 and 435 may play a role in its poor response to activation by phosphorylation.

Annotation

Gene Ontology Annotations
Objects Annotated
Objects referenced in this article

Additional Information

 
CRRD Object Information
CRRD ID: 729717
Created: 2003-11-26
Species: All species
Last Modified: 2004-05-25
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.