Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
47
pubmed:dateCreated
2009-11-25
pubmed:abstractText
Ammodytoxins are presynaptically neurotoxic snake venom group IIA secreted phospholipase A(2) enzymes that interact specifically with calmodulin in the cytosol of nerve cells. We show that calmodulin behaves as an activator of ammodytoxin under both nonreducing and reducing (cytosol-like) conditions by stimulating its enzymatic activity up to 21-fold. Kinetic analysis, using a general modifier mechanism, and surface plasmon resonance measurements reveal that calmodulin influences both the catalytic and the vesicle binding properties of the enzyme without affecting its calcium binding properties. The equilibrium dissociation constant of the ammodytoxin-calmodulin complex under cytosol-like conditions is in the low nanomolar range (3 nM), while under nonreducing conditions, the binding affinity is in the subnanomolar range (0.07-0.18 nM). Upon exposure to cytosol-like conditions, ammodytoxin undergoes a slow hysteretic transition to a less active state. Calmodulin stabilizes the conformation of ammodytoxin and thereby restores its activity. These results provide insights into the neurotoxic action of ammodytoxins and the mechanisms involved in the regulation of secreted phospholipase A(2) activity within the cytosol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11319-28
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Calmodulin is a nonessential activator of secretory phospholipase A(2).
pubmed:affiliation
Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't