Nucleoside triphosphate pentose ring impact on CFTR gating and hydrolysis

FEBS Letters

Aleksandrov, Andrei A.¹  Aleksandrov, Luba¹  R. Riordan, John¹ 

[1] Mayo Foundation and Mayo Clinic Scottsdale, S.C. Johnson Medical Research Center, 13400 E. Shea Blvd., Scottsdale, AZ 85259, USA

关键词: Cystic fibrosis transmembrane conductance regulator;    Gating kinetics;    ATP hydrolysis;    CFTR;    cystic fibrosis transmembrane conductance regulator;    NBD;    nucleotide binding domain;    PKA;    protein kinase A;   

DOI  :  10.1016/S0014-5793(02)02698-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown