ABCC7 p.Phe1068Met
| Predicted by SNAP2: | A: D (80%), C: D (63%), D: D (95%), E: D (91%), G: D (91%), H: D (85%), I: D (85%), K: D (91%), L: D (80%), M: D (71%), N: D (85%), P: D (95%), Q: D (85%), R: D (91%), S: D (85%), T: D (91%), V: D (85%), W: D (91%), Y: N (78%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: N, Y: N, |
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[hide] Relationship between nucleotide binding and ion ch... J Physiol. 2009 Jun 15;587(Pt 12):2875-86. Epub 2009 Apr 29. Aleksandrov AA, Cui L, Riordan JR
Relationship between nucleotide binding and ion channel gating in cystic fibrosis transmembrane conductance regulator.
J Physiol. 2009 Jun 15;587(Pt 12):2875-86. Epub 2009 Apr 29., 2009-06-15 [PMID:19403599]
Abstract [show]
We have employed rate-equilibrium free energy relationship (REFER) analysis to characterize the dynamic events involved in the allosteric regulation of cystic fibrosis transmembrane conductance regulator (CFTR) function. A wide range of different hydrolysable and poorly hydrolysable nucleoside triphosphates were used to elucidate the role of ATP hydrolysis in CFTR function. The linearity of the REFER plots and Phi values near unity for all ligands tested implies that CFTR channel gating is a reversible thermally driven process with all structural reorganization in the binding site(s) completed prior to channel opening. This is consistent with the requirement for nucleotide binding for channel opening. However, the channel structural transition from the open to the closed state occurs independently of any events in the binding sites. Similar results were obtained on substitution of amino acids at coupling joints between both nucleotide binding domains (NBD) and cytoplasmic loops (CL) in opposite halves of the protein, indicating that any structural reorganization there also had occurred in the channel closed state. The fact that fractional Phi values were not observed in either of these distant sites suggests that there may not be a deterministic 'lever-arm' mechanism acting between nucleotide binding sites and the channel gate. These findings favour a stochastic coupling between binding and gating in which all structural transitions are thermally driven processes. We speculate that increase of channel open state probability is due to reduction of the number of the closed state configurations available after physical interaction between ligand bound NBDs and the channel.
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No. Sentence Comment
142 All mutants at position 1068 have mean open times narrowly distributedaround220mswithmeanclosedtimesranging widely from 100 ms for F1068M to 3.1 s for F1068W.
X
ABCC7 p.Phe1068Met 19403599:142:131
status: NEW