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Nucleoside triphosphate pentose ring impact on CFTR gating and hydrolysis
Author(s) -
Aleksandrov Andrei A.,
Aleksandrov Luba,
R. Riordan John
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02698-4
Subject(s) - cystic fibrosis transmembrane conductance regulator , chemistry , atp hydrolysis , gating , adenosine triphosphate , cyclic nucleotide binding domain , biochemistry , ribonucleotide , protein subunit , biophysics , nucleotide , enzyme , stereochemistry , biology , atpase , gene
Alterations in the pentose ring of ATP have a major impact on cystic fibrosis transmembrane conductance regulator (CFTR) function. Both 2′‐ and 3′‐deoxy‐ATP (dATP) accelerate ion channel openings and stabilize open channel structure better than ATP. Purified wild‐type CFTR hydrolyzes dATP. The apparent first‐order rate constants for hydrolysis at low substrate concentration are the same for dATP and ATP. This suggests that product release and/or relaxation of the enzyme structure to the initial ligand free state is the rate‐limiting step in the CFTR hydrolytic cycle. Circumvention of the normal requirement for protein kinase A phosphorylation of the R‐domain for channel activation implies that the impact of the deoxyribonucleotide interaction with the nucleotide binding domains is transmitted to the channel‐forming elements of the protein more readily than that of the ribonucleotide.