Title : Residue 33 of human equilibrative nucleoside transporter 2 is a functionally important component of both the dipyridamole and nucleoside binding sites.

Pub. Date : 2005 Apr

PMID : 15644498






8 Functional Relationships(s)
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Protein Name
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1 Residue 33 of human equilibrative nucleoside transporter 2 is a functionally important component of both the dipyridamole and nucleoside binding sites. Dipyridamole solute carrier family 29 member 2 Homo sapiens
2 Human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) differ functionally in that hENT2 generally displays lower affinity for its nucleoside permeants and is less sensitive to inhibition by the coronary vasodilators dilazep and dipyridamole. Dipyridamole solute carrier family 29 member 2 Homo sapiens
3 Human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) differ functionally in that hENT2 generally displays lower affinity for its nucleoside permeants and is less sensitive to inhibition by the coronary vasodilators dilazep and dipyridamole. Dipyridamole solute carrier family 29 member 2 Homo sapiens
4 In previous work, we demonstrated that mutation of residues 33 (Met versus Ile) of hENT1 and hENT2 altered sensitivity to dilazep and dipyridamole and that the hENT2 mutant (I33M) displayed a K(m) value for uridine that was lower than that of hENT2 and similar to that of hENT1 (J Biol Chem 277:395-401, 2002). Dipyridamole solute carrier family 29 member 2 Homo sapiens
5 hENT2-I33M and I33C displayed increased sensitivities to dipyridamole compared with wild-type hENT2, hENT2-I33A, and hENT2-I33S, suggesting interaction of the sulfur atom of Met and Cys with aromatic moieties on dipyridamole. Dipyridamole solute carrier family 29 member 2 Homo sapiens
6 hENT2-I33M and I33C displayed increased sensitivities to dipyridamole compared with wild-type hENT2, hENT2-I33A, and hENT2-I33S, suggesting interaction of the sulfur atom of Met and Cys with aromatic moieties on dipyridamole. Dipyridamole solute carrier family 29 member 2 Homo sapiens
7 hENT2-I33C was inhibited by the membrane-impermeant sulfhydryl reactive reagent p-chloromercuribenzyl sulfonate, and uridine, adenosine, and dipyridamole protected against inhibition. Dipyridamole solute carrier family 29 member 2 Homo sapiens
8 Our results indicated that residue 33 resides in an extracellular domain as predicted by the current hENT2 topology model and suggested that it is a functionally important component of both the permeant and dipyridamole binding sites. Dipyridamole solute carrier family 29 member 2 Homo sapiens