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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1983-10-8
pubmed:abstractText
The binding of 16 derivatives of cAMP to the surface of Dictyostelium discoideum cells was analyzed. The binding affinity is strongly reduced (more than 14.5 kJ/mol) if a cAMP derivative is no longer able to form a hydrogen bond at N6H2, or at O3'. Decreasing polarity of the base moiety is closely correlated to increasing binding affinity to the cAMP receptor (r = 0.98, p less than 0.1%). Based on these results we propose that cAMP is bound to the receptor via hydrogen bonds at N6H2 and O3', and that the adenine moiety is bound in a hydrophobic cleft of the receptor. A stereospecific interaction between the receptor and the phosphate moiety of cAMP has not been observed. The first detectable response of D. discoideum cells to cAMP is an increase of intracellular cGMP levels. A close correlation exists between the binding affinity of the cAMP derivatives and the potency to induce a cGMP response (r = 0.97, p less than 0.01%). There are two exceptions; both derivatives are modified in the exocyclic oxygen atoms of the phosphate moiety (sulfur in equatorial position or dimethylamino in apical position). These derivatives bind with approximately the same affinity as their stereoisomers (respectively sulfur in apical or dimethylamino in equatorial position), but in contrast to their stereoisomers, they do not induce elevations of cGMP levels. This suggests that, in addition to the binding interactions mentioned above, activation of the receptor requires a stereospecific interaction between the receptor and the phosphate moiety of cAMP. Quantum-chemical calculations by Van Ool and Buck (Van Ool, P. J. J. M., and Buck, H. M. (1982) Eur. J. Biochem. 121, 329-334) suggest that this activating interaction is a covalent bond between cAMP and the receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
258
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9636-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Binding of cAMP derivatives to Dictyostelium discoideum cells. Activation mechanism of the cell surface cAMP receptor.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't