ABCB1 p.Val991Cys
[switch to full view]Comments [show]
None has been submitted yet.
PMID: 12609990
[PubMed]
Loo TW et al: "Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding."
No.
Sentence
Comment
85
Membranes prepared from HEK 293 cells expressing mutants P350C(TM6)/ A935C(TM11), P350C(TM6)/G939C(TM11), or P350C(TM6)/V991C- (TM12) were preincubated for 10 min at 21 °C with no drug, 1 mM progesterone, 0.1 mM cyclosporin A, 5 mM colchicine, or 1 mM demecolcine.
X
ABCB1 p.Val991Cys 12609990:85:120
status: NEW92 In mutant P350C(TM6)/V991C- (TM12), the drug substrates colchicine, demecolcine, and progesterone were equally effective in promoting cross-linking.
X
ABCB1 p.Val991Cys 12609990:92:21
status: NEW107 Accordingly, we tested whether the drug substrates colchicine, demecolcine, progesterone, cis-(Z)-flupenthixol, verapamil, or vinblastine stimulated the ATPase activities of histidine-tagged mutants P350C(TM6)/A935C- (TM11), P350C(TM6)/G939C(TM11), and P350C(TM6)/V991C- (TM12).
X
ABCB1 p.Val991Cys 12609990:107:264
status: NEW124 In the presence of drug substrate (progesterone), TM segments 11 and 12 undergo rotational and/or lateral movements so that cross-linking can occur between P350C and V991C (black ball) in TM12 and with A935C (red ball) and G939C (turquoise ball) in TM11.
X
ABCB1 p.Val991Cys 12609990:124:166
status: NEW135 The presence of progesterone, however, promoted cross-linking of residue P350C(TM6) with two residues in TM 11 (A935C and G939C) and to residue V991C in TM12.
X
ABCB1 p.Val991Cys 12609990:135:144
status: NEW139 Therefore, the presence of drug substrate (progesterone) likely causes a slight rotation/rearrangement of TM12 relative to TM6 such that residue V991C comes closer to P350C.
X
ABCB1 p.Val991Cys 12609990:139:145
status: NEW
PMID: 9261097
[PubMed]
Loo TW et al: "Drug-stimulated ATPase activity of human P-glycoprotein requires movement between transmembrane segments 6 and 12."
No.
Sentence
Comment
80
We also tested mutants F335C/L976C, L339C/S979C, F343C/F983C, G347C/A987C, and S351C/ V991C for cross-linking since they were predicted to lie on opposing faces of TM6 and TM12 modeled in a right-handed coiled-coil.
X
ABCB1 p.Val991Cys 9261097:80:86
status: NEW