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PDBsum entry 4m1m
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PDB id:
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Hydrolase
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Title:
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Corrected structure of mouse p-glycoprotein
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Structure:
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Multidrug resistance protein 1a. Chain: a, b. Synonym: atp-binding cassette sub-family b member 1a, mdr1a, multidrug resistance protein 3, p-glycoprotein 3. Engineered: yes
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: abcb1a, abcb4, mdr1a, mdr3, pgy-3, pgy3. Expressed in: komagataella pastoris. Expression_system_taxid: 4922
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Resolution:
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3.80Å
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R-factor:
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0.217
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R-free:
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0.267
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Authors:
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J.Li,K.F.Jaimes,S.G.Aller
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Key ref:
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J.Li
et al.
(2014).
Refined structures of mouse P-glycoprotein.
Protein Sci,
23,
34-46.
PubMed id:
DOI:
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Date:
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03-Aug-13
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Release date:
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13-Nov-13
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PROCHECK
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Headers
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References
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P21447
(MDR1A_MOUSE) -
ATP-dependent translocase ABCB1 from Mus musculus
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Seq:
Struc:
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1276 a.a.
1188 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 4 residue positions (black
crosses)
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Enzyme class 1:
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E.C.7.6.2.1
- P-type phospholipid transporter.
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Reaction:
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ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2
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ATP
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+
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H2O
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+
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phospholipidSide 1
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=
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ADP
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+
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phosphate
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+
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phospholipidSide 2
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Enzyme class 2:
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E.C.7.6.2.2
- ABC-type xenobiotic transporter.
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Reaction:
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ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2
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ATP
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+
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H2O
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+
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xenobioticSide 1
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=
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ADP
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+
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phosphate
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+
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xenobioticSide 2
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Protein Sci
23:34-46
(2014)
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PubMed id:
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Refined structures of mouse P-glycoprotein.
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J.Li,
K.F.Jaimes,
S.G.Aller.
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ABSTRACT
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The recently determined C. elegans P-glycoprotein (Pgp) structure revealed
significant deviations compared to the original mouse Pgp structure, which
suggested possible misinterpretations in the latter model. To address this
concern, we generated an experimental electron density map from
single-wavelength anomalous dispersion phasing of an original mouse Pgp dataset
to 3.8 Å resolution. The map exhibited significantly more detail compared to
the original MAD map and revealed several regions of the structure that required
de novo model building. The improved drug-free structure was refined to 3.8 Å
resolution with a 9.4 and 8.1% decrease in Rwork and Rfree , respectively,
(Rwork = 21.2%, Rfree = 26.6%) and a significant improvement in
protein geometry. The improved mouse Pgp model contains ∼95% of residues in
the favorable Ramachandran region compared to only 57% for the original model.
The registry of six transmembrane helices was corrected, revealing amino acid
residues involved in drug binding that were previously unrecognized. Registry
shifts (rotations and translations) for three transmembrane (TM)4 and TM5 and
the addition of three N-terminal residues were necessary, and were validated
with new mercury labeling and anomalous Fourier density. The corrected position
of TM4, which forms the frame of a portal for drug entry, had backbone atoms
shifted >6 Å from their original positions. The drug translocation pathway
of mouse Pgp is 96% identical to human Pgp and is enriched in aromatic residues
that likely play a collective role in allowing a high degree of polyspecific
substrate recognition.
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