P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK

O'Mara, Megan L. and Tieleman, D. Peter (2007) P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK. FEBS Letters, 581 22: 4217-4222. doi:10.1016/j.febslet.2007.07.069


Author O'Mara, Megan L.
Tieleman, D. Peter
Title P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK
Journal name FEBS Letters   Check publisher's open access policy
ISSN 0014-5793
1873-3468
Publication date 2007-09
Sub-type Article (original research)
DOI 10.1016/j.febslet.2007.07.069
Volume 581
Issue 22
Start page 4217
End page 4222
Total pages 6
Editor F. Wieland
Place of publication Amsterdam, The Netherlands
Publisher Elsevier Science B. V.
Language eng
Subject 03 Chemical Sciences
06 Biological Sciences
0601 Biochemistry and Cell Biology
Formatted abstract
We exploit the biochemical and sequence similarity between Staphylococcus aureus Sav1866 and P-glycoprotein to develop a homology model of P-glycoprotein representing an ATP-bound state, which captures the major features of the low-resolution EM structure and is consistent with cysteine mutagenesis studies. Using insights from the MalK crystal structures and BtuCD simulations, we model two nucleotide-free conformations. Conformational changes are characterized by pincering rigid-body rotations of the nucleotide-binding domains, inducing transmembrane domain reorganizations which correspond to the two lowest frequency normal modes of the protein. These conformations (see supplementary material) may characterize some of the major steps in the nucleotide catalytic cycle.
Keyword Homology modeling
MalK
ATP-bound states
P-glycoprotein
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes FEBS: Federation of European Biochemical Societies

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 07 Jan 2010, 13:58:39 EST by Rosalind Blair on behalf of Faculty of Science