ABCB2 p.Glu3Asp
| Predicted by SNAP2: | A: N (72%), C: N (72%), D: N (82%), F: N (57%), G: N (61%), H: N (72%), I: N (61%), K: N (66%), L: N (57%), M: N (72%), N: N (78%), P: D (53%), Q: N (82%), R: N (57%), S: N (78%), T: N (78%), V: N (66%), W: N (57%), Y: N (61%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Catalytic site modifications of TAP1 and TAP2 and ... J Biol Chem. 2006 Dec 29;281(52):39839-51. Epub 2006 Oct 26. Perria CL, Rajamanickam V, Lapinski PE, Raghavan M
Catalytic site modifications of TAP1 and TAP2 and their functional consequences.
J Biol Chem. 2006 Dec 29;281(52):39839-51. Epub 2006 Oct 26., [PMID:17068338]
Abstract [show]
The transporter associated with antigen processing (TAP), a member of the ATP binding cassette (ABC) family of transmembrane transporters, transports peptides across the endoplasmic reticulum membrane for assembly of major histocompatibility complex class I molecules. Two subunits, TAP1 and TAP2, are required for peptide transport, and ATP hydrolysis by TAP1.TAP2 complexes is important for transport activity. Two nucleotide binding sites are present in TAP1.TAP2 complexes. Compared with other ABC transporters, the first nucleotide binding site contains non-consensus catalytic site residues, including Asp(668) in the Walker B region of TAP1 (in place of a highly conserved glutamic acid), and Gln(701) in the switch region of TAP1 (in place of a highly conserved histidine). At the second nucleotide binding site, a glutamic acid (TAP2 Glu(632)) follows the Walker B motif, and the switch region contains a histidine (TAP2 His(661)). We found that alterations at Glu(632) and His(661) of TAP2 significantly reduced peptide translocation and/or TAP-induced major histocompatibility complex class I surface expression. Alterations of TAP1 Asp(668) alone or in combination with TAP1 Gln(701) had only small effects on TAP activity. Thus, the naturally occurring Asp(668) and Gln(701) alterations of TAP1 are likely to contribute to attenuated catalytic activity at the first nucleotide binding site (the TAP1 site) of TAP complexes. Due to its enhanced catalytic activity, the second nucleotide binding site (the TAP2 site) appears to be the main site driving peptide transport. A mechanistic model involving one main active site is likely to apply to other ABC transporters that have an asymmetric distribution of catalytic site residues within the two nucleotide binding sites.
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No. Sentence Comment
313 These include ABCC1-6 and ABCC10-11 (multidrug resistance proteins), ABCC8 and ABCC9 (SUR1 and SUR2) that all contain Walker B Glu 3 Asp substitutions in their NBD1, and NBD1 of ABCC7 (cystic fibrosis transmembrane conductance regulator, which has a Walker B Glu 3 Ser substitution).
X
ABCB2 p.Glu3Asp 17068338:313:127
status: NEW312 These include ABCC1-6 and ABCC10-11 (multidrug resistance proteins), ABCC8 and ABCC9 (SUR1 and SUR2) that all contain Walker B Glu 3 Asp substitutions in their NBD1, and NBD1 of ABCC7 (cystic fibrosis transmembrane conductance regulator, which has a Walker B Glu 3 Ser substitution).
X
ABCB2 p.Glu3Asp 17068338:312:127
status: NEW310 These include ABCC1-6 and ABCC10-11 (multidrug resistance proteins), ABCC8 and ABCC9 (SUR1 and SUR2) that all contain Walker B Glu 3 Asp substitutions in their NBD1, and NBD1 of ABCC7 (cystic fibrosis transmembrane conductance regulator, which has a Walker B Glu 3 Ser substitution).
X
ABCB2 p.Glu3Asp 17068338:310:127
status: NEW