ABCC1 p.Glu631Gln
| Predicted by SNAP2: | A: N (87%), C: N (93%), D: N (97%), F: N (57%), G: N (82%), H: N (93%), I: N (82%), K: N (82%), L: N (82%), M: N (72%), N: N (93%), P: N (72%), Q: N (97%), R: N (93%), S: N (93%), T: N (93%), V: N (82%), W: N (66%), Y: N (61%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D, |
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[hide] Homology modeling of breast cancer resistance prot... J Struct Biol. 2008 Apr;162(1):63-74. Epub 2007 Dec 15. Hazai E, Bikadi Z
Homology modeling of breast cancer resistance protein (ABCG2).
J Struct Biol. 2008 Apr;162(1):63-74. Epub 2007 Dec 15., [PMID:18249138]
Abstract [show]
BCRP (also known as ABCG2, MXR, and ABC-P) is a member of the ABC family that transports a wide variety of substrates. BCRP is known to play a key role as a xenobiotic transporter. Since discovering its role in multidrug resistance, considerable efforts have been made in order to gain deeper understanding of BCRP structure and function. The recent study was aimed at predicting BCRP structure by creating a homology model. Based on sequence similarity with known structures of full-length, NB and TM domain of ABC transporters, TM, NB, and linker regions of BCRP were defined. The NB domain of BCRP was modeled using MalK as a template. Based on secondary structure prediction of BCRP and comparison of the transmembrane connecting regions of known structures of ABC transporters, the TM domain arrangement of BCRP was established and was found to resemble to that of the recently published crystal structure of Sav1866. Thus, an initial alignment of TM domain of BCRP was established using Sav1866 as a template. This alignment was subsequently refined using constrains derived from secondary structure and TM predictions and the final model was built. Finally, the complete homodimer ABCG2 model was generated using Sav1866 as template. Furthermore, known ligands of BCRP were docked to our model in order to define possible binding sites. The results of molecular dockings of known BCRP substrates to the BCRP model were in agreement with recently published experimental data indicating multiple binding sites in BCRP.
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No. Sentence Comment
97 Table 1 Sequence identity and similarity between BCRP and available templates PDB ID Title Identity Similarity Ligand Nucleotide binding domain 1Q1B Crystal structure of E. coli MalK in the nucleotide-free form 31.00 51.00 No 1Q12 Crystal structure of the ATP-bound E. coli MalK 31.00 51.00 ATP 1OXS Crystal structure of GlcV, the ABC-ATPase of the glucose ABC transporter from Sulfolobus solfataricus 28.00 49.00 I- 1MV5 Crystal structure of LmrA ATP-binding domain 28.00 50.00 ATP/ADP 2FF7 The ABC-ATPase of the ABC-transporter HlyB in the ADP bound state 29.00 50.00 ADP 1MT0 ATP-binding domain of haemolysin B from E. coli 29.00 49.00 Sulphate 1OXX Crystal structure of GlcV, the ABC-ATPase of the glucose ABC transporter from Sulfolobus solfataricus 27.00 49.00 I- 1L2T Dimeric structure of MJ0796, a bacterial ABC transporter cassette 27.00 50.00 ATP/isopropanol 2FGK Crystal structure of the ABC-cassette E631Q mutant of HlyB with bound ATP 29.00 49.00 ATP 1XEF Crystal structure of the ATP/Mg2+ bound composite dimer of HlyB-NBD 29.00 49.00 ATP 1G29 Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter 26.00 46.00 Pyrophosphate/ dioxane 1B0U ATP-binding subunit of the histidine permease from Salmonella Typhimurium 25.00 52.00 ATP 1G6H Crystal structure of the ADP conformation of Mj1267 22.00 43.00 ADP 1R0W Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) apo 24.00 42.00 Acetic acid 1JJ7 Crystal structure of the C-terminal ATPase domain of human TAP1 25.00 44.00 ADP 2HYD Multidrug ABC transporter SAV1866 28.00 49.00 ADP 2CBZ Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 19.20 32.40 ATP The templates selected for modeling BCRP structure are indicated in bold.
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ABCC1 p.Glu631Gln 18249138:97:912
status: NEW[hide] Engineering ATPase activity in the isolated ABC ca... J Biol Chem. 2006 Sep 15;281(37):27471-80. Epub 2006 Jul 24. Ernst R, Koch J, Horn C, Tampe R, Schmitt L
Engineering ATPase activity in the isolated ABC cassette of human TAP1.
J Biol Chem. 2006 Sep 15;281(37):27471-80. Epub 2006 Jul 24., [PMID:16864587]
Abstract [show]
The human transporter associated with antigen processing (TAP) translocates antigenic peptides from the cytosol into the endoplasmic reticulum lumen. The functional unit of TAP is a heterodimer composed of the TAP1 and TAP2 subunits, both of which are members of the ABC-transporter family. ABC-transporters are ATP-dependent pumps, channels, or receptors that are composed of four modules: two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Although the TMDs are rather divergent in sequence, the NBDs are conserved with respect to structure and function. Interestingly, the NBD of TAP1 contains mutations at amino acid positions that have been proposed to be essential for catalytic activity. Instead of a glutamate, proposed to act as a general base, TAP1 contains an aspartate and a glutamine instead of the conserved histidine, which has been suggested to act as the linchpin. We used this degeneration to evaluate the individual contribution of these two amino acids to the ATPase activity of the engineered TAP1-NBD mutants. Based on our results a catalytic hierarchy of these two fundamental amino acids in ATP hydrolysis of the mutated TAP1 motor domain was deduced.
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No. Sentence Comment
43 For the NBD of HlyB, a mutation of the corresponding histidine to alanine (H662A) eliminated ATPase activity as well, whereas residual ATPase activity was detected in the glutamate to glutamine mutant (E631Q) (30).
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ABCC1 p.Glu631Gln 16864587:43:202
status: NEW