ABCB1 p.Ser43Gly
| Predicted by SNAP2: | A: N (97%), C: D (59%), D: D (75%), E: D (75%), F: D (71%), G: N (72%), H: D (71%), I: D (66%), K: D (75%), L: D (71%), M: N (53%), N: D (63%), P: D (75%), Q: D (71%), R: D (75%), T: N (66%), V: D (66%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: D, G: N, H: D, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Mutational analysis of conserved aromatic residues... FEBS Lett. 2007 Jan 23;581(2):301-8. Epub 2007 Jan 3. Carrier I, Urbatsch IL, Senior AE, Gros P
Mutational analysis of conserved aromatic residues in the A-loop of the ABC transporter ABCB1A (mouse Mdr3).
FEBS Lett. 2007 Jan 23;581(2):301-8. Epub 2007 Jan 3., [PMID:17214987]
Abstract [show]
The A-loop is a recently described conserved region in the NBDs of ABC transporters [Ambudkar, S.V., Kim, I.-W., Xia, D. and Sauna, Z.E. (2006) The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding. FEBS Lett. 580, 1049-1055; Kim, I.W., Peng, X.H., Sauna, Z.E., FitzGerald, P.C., Xia, D., Muller, M., Nandigama, K. and Ambudkar, S.V. (2006) The conserved tyrosine residues 401 and 1044 in ATP sites of human P-glycoprotein are critical for ATP binding and hydrolysis: evidence for a conserved subdomain, the A-loop in the ATP-binding cassette. Biochemistry 45, 7605-7616]. In mouse P-glycoprotein (Abcb1a), the aromatic residue of the A-loop in both NBDs is a tyrosine: Y397 in NBD1 and Y1040 in NBD2. Another tyrosine residue (618 in NBD1 and 1263 in NBD2) also appears to lie in proximity to the ATP molecule. We have mutated residues Y397, Y618, Y1040, and Y1263 to tryptophan and analyzed the effect of these substitutions on transport properties, ATP binding, and ATP hydrolysis by Abcb1a (mouse Mdr3). Y618W and Y1263W enzymes had catalytic characteristics similar to WT Abcb1a. On the other hand, Y397W and Y1040W showed impaired transport and greatly reduced ATPase activity, including a approximately 10-fold increase in Km for MgATP. Thus, Y397 and Y1040 play an important role in Abcb1a catalysis.
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No. Sentence Comment
95 D551/ D1196 D178 Q100 Q471/ Q1114 K429/K1072 G423/G1066 K45 G39 Y397/Y1040 PO O O PO O O P O O O N N N N N Ser-41 Wat-500 Wat-443 NG426/G1069 C427/C1070 G428/G1071 K429/K1072 D551/D1196 Q471/Q1114 E552/E1197 H583/H1228 S425/S1068 S430/S1073 T431/T1074 O- Wat-445 O- Wat-407 2- Wat-437 Wat-415 Lys-45 Gly-44 Ser-43 Gly-42 Asp-178 His-211Glu-179Gln-100 O O O K401/R1043 Q531/Q1176 Wat-488 His-19 Gln-158 Ser-46 Thr-47 A B C D Y16 O N N N N N Wat-644 Wat-538 Wat-424 Wat-467 Y397/Y1040 OTyr-16 L H V I D L H K R Y VQ F SGF V F N Y HisP mMdr3 hMDR1 V T FGE V V F N Y 160(208)/279 GG H .
X
ABCB1 p.Ser43Gly 17214987:95:307
status: NEW93 D551/ D1196 D178 Q100 Q471/ Q1114 K429/K1072 G423/G1066 K45 G39 Y397/Y1040 P O O O P O O O P O O O N N N N N Ser-41 Wat-500 Wat-443 N G426/G1069 C427/C1070 G428/G1071 K429/K1072 D551/D1196 Q471/Q1114 E552/E1197 H583/H1228 S425/S1068 S430/S1073 T431/T1074 O - Wat-445 O - Wat-407 2- Wat-437 Wat-415 Lys-45 Gly-44 Ser-43 Gly-42 Asp-178 His-211 Glu-179 Gln-100 O O O K401/R1043 Q531/Q1176 Wat-488 His-19 Gln-158 Ser-46 Thr-47 A B C D Y16 O N N N N N Wat-644 Wat-538 Wat-424 Wat-467 Y397/Y1040 O Tyr-16 L H V I D L H K R Y VQ F SGF V F N Y HisP mMdr3 hMDR1 V T FGE V V F N Y 160(208)/279 GG H .
X
ABCB1 p.Ser43Gly 17214987:93:312
status: NEW