@entity436 antagonists appear to access two distinct binding sites on different members of this receptor family. One class of @entity16952 antagonists has been suggested to bind to a site accessible from the cytoplasm while a second class did not bind to this site. In this report, we demonstrate that antagonists representing a variety of structural classes bind to two distinct allosteric sites on @entity16952 . The effects of pairs of low-molecular weight and/or chemokine @entity16952 antagonists were evaluated on @entity14420 - and @entity14421 -induced responses of @entity1 @entity16952 (+) T cells. This provided an initial grouping of the antagonists into sets which appeared to bind to distinct binding sites. Binding studies were then performed with radioligands from each set to confirm these groupings. Some novel receptor theory was developed to allow the interpretation of the effects of the antagonist combinations. The theory indicates that, generally, the concentration-ratio of a pair of competing allosteric modulators is maximally the sum of their individual effects while that of two modulators acting at different sites is likely to be greater than their sum. The low-molecular weight antagonists could be grouped into two sets on the basis of the functional and binding experiments. The antagonistic chemokines formed a third set whose behaviour was consistent with that of simple competitive antagonists. These studies indicate that there are two allosteric regulatory sites on @entity16952 .

Antagonism of @entity1 CC- XXXX 4 can be achieved through three distinct binding sites on the receptor.

@entity1 :: ('9606', 'Species') :: ['human'] @entity14421 :: ('6367', 'Gene') :: ['CCL22'] @entity14420 :: ('6361', 'Gene') :: ['CCL17'] @entity16952 :: ('1233', 'Gene') :: ['CCR4'] @entity436 :: ('7852', 'Gene') :: ['Chemokine receptor']
@entity436 :: (7852,Gene) :: ['chemokine receptor']
