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FEBS Lett. 2002 May 8;518(1-3):183-8.

Nucleoside triphosphate pentose ring impact on CFTR gating and hydrolysis.

Author information

1
Mayo Foundation and Mayo Clinic Scottsdale, S.C. Johnson Medical Research Center, 13400 E. Shea Blvd., Scottsdale, AZ 85259, USA. aleksand@mayo.edu

Abstract

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.

PMID:
11997043
[Indexed for MEDLINE]
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