Document Detail


Physicochemical changes in phosphorylase kinase associated with its activation.
MedLine Citation:
PMID:  18794211     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphorylase kinase (PhK) regulates glycogenolysis through its Ca(2+)-dependent phosphorylation and activation of glycogen phosphorylase. The activity of PhK increases dramatically as the pH is raised from 6.8 to 8.2 (denoted as upward arrow pH), but Ca(2+) dependence is retained. Little is known about the structural changes associated with PhK's activation by upward arrow pH and Ca(2+), but activation by both mechanisms is mediated through regulatory subunits of the (alphabetagammadelta)(4) PhK complex. In this study, changes in the structure of PhK induced by upward arrow pH and Ca(2+) were investigated using second derivative UV absorption, synchronous fluorescence, circular dichroism spectroscopy, and zeta potential analyses. The joint effects of Ca(2+) and upward arrow pH on the physicochemical properties of PhK were found to be interdependent, with their effects showing a strong inflection point at pH approximately 7.6. Comparing the properties of the conformers of PhK present under the condition where it would be least active (pH 6.8 - Ca(2+)) versus that where it would be most active (pH 8.2 + Ca(2+)), the joint activation by upward arrow pH and Ca(2+) is characterized by a relatively large increase in the content of sheet structure, a decrease in interactions between helix and sheet structures, and a dramatically less negative electrostatic surface charge. A model is presented that accounts for the interdependent activating effects of upward arrow pH and Ca(2+) in terms of the overall physicochemical properties of the four PhK conformers described herein, and published data corroborating the transitions between these conformers are tabulated.
Authors:
Weiya Liu; Timothy S Priddy; Gerald M Carlson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-15
Journal Detail:
Title:  Protein science : a publication of the Protein Society     Volume:  17     ISSN:  1469-896X     ISO Abbreviation:  Protein Sci.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2009-02-10     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9211750     Medline TA:  Protein Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2111-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Circular Dichroism
Enzyme Activation
Female
Hydrogen-Ion Concentration
Phosphorylase Kinase / chemistry*,  metabolism*
Protein Structure, Secondary
Protein Structure, Tertiary
Rabbits
Spectrometry, Fluorescence
Spectrophotometry, Ultraviolet
Static Electricity
Surface Properties
Grant Support
ID/Acronym/Agency:
DK32953/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
7440-70-2/Calcium; EC 2.7.1.19/Phosphorylase Kinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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