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Bioelectronic Measurement of Target Engagement to a Membrane-Bound Transporter

Autor: Martinez William Emerson, Gutierrez M Gertrude, Joseph G. McGivern, Monica M. Lozano, Rodrigo Sierra Chavera, Leo Mok, Ngo Yin Wong, Jaime E. Arenas, Wan-Chen Lin

Publikováno v: SLAS Discovery. 26:1004-1013

The ability to detect and characterize drug binding to a target protein is of high priority in drug discovery research. However, there are inherent challenges when the target of interest is an integral membrane protein (IMP). Assuming successful puri

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e4383b314cd2e2c35465900c105dfff6
https://doi.org/10.1177/24725552211013067

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Substrate-induced conformational changes in the nucleotide-binding domains of lipid bilayer–associated P-glycoprotein during ATP hydrolysis

Autor: Anukriti Singh, Ina L. Urbatsch, Gregory A. Fendley, Maria E. Zoghbi, Leo Mok, Guillermo A. Altenberg, Douglas J. Swartz

Publikováno v: The Journal of biological chemistry, vol 292, iss 50

P-glycoprotein (Pgp) is an efflux pump important in multidrug resistance of cancer cells and in determining drug pharmacokinetics. Pgp is a prototype ATP-binding cassette transporter with two nucleotide-binding domains (NBDs) that bind and hydrolyze

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9cc751d6378f16f80e18e39ca84b80b
https://doi.org/10.1074/jbc.m117.814186

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Interactions and cooperativity between P-glycoprotein structural domains determined by thermal unfolding provides insights into its solution structure and function

Autor: Christie G. Brouillette, Qingxian Zhou, Douglas J. Swartz, Leo Mok, Anukriti Singh, Ina L. Urbatsch, Zhengrong Yang

Publikováno v: Biochim Biophys Acta Biomembr

Structural changes in mouse P-glycoprotein (Pgp) induced by thermal unfolding were studied by differential scanning calorimetry (DSC), circular dichroism and fluorescence spectroscopy to gain insight into the solution conformation(s) of this ABC tran

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10ef252810d955393a0e2020018b68d0
https://doi.org/10.1016/j.bbamem.2016.10.009

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ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells

Autor: Shui-Pang Tam, Monika Vasa, Giovanna Chimini, Leo Mok, Roger G. Deeley

Publikováno v: American Journal of Physiology-Cell Physiology
American Journal of Physiology-Cell Physiology, American Physiological Society, 2006, 291 (3), pp.C490-502. ⟨10.1152/ajpcell.00055.2006⟩
American Journal of Physiology-Cell Physiology, 2006, 291 (3), pp.C490-502. ⟨10.1152/ajpcell.00055.2006⟩

ATP Binding Cassette (ABC) transporter, ABCA1, plays a pivotal role in reverse cholesterol transport by mediating the cellular efflux of phospholipid and cholesterol. Studies using intact cells strongly suggest that ABCA1 acts as a phospholipid flopp

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::598d28d1733e9a14b3632184b9297afa
https://doi.org/10.1152/ajpcell.00055.2006

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Directed evolution of P-glycoprotein cysteines reveals site-specific, non-conservative substitutions that preserve multidrug resistance

Autor: Guillermo A. Altenberg, Anukriti Singh, Douglas J. Swartz, Sri K. Botta, Ina L. Urbatsch, Leo Mok

Publikováno v: Bioscience Reports, Vol 34, Iss 3, p e00116 (2014)
Bioscience Reports

Pgp (P-glycoprotein) is a prototype ABC (ATP-binding-cassette) transporter involved in multidrug resistance of cancer. We used directed evolution to replace six cytoplasmic Cys (cysteine) residues in Pgp with all 20 standard amino acids and selected

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efd5c63c212d3ee1f3b0200139d59985
http://www.bioscirep.org/bsr/034/e116/bsr034e116.htm

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Susceptibility of Epithelial Cells to Pseudomonas aeruginosa Invasion and Cytotoxicity Is Upregulated by Hepatocyte Growth Factor

Autor: Leo Mok, Vicky Vallas, Michael G. Roth, Suzanne M. J. Fleiszig, Keith E. Mostov, Cindy H. Jun, Daniel F. Balkovetz

Publikováno v: Infection and Immunity. 66:3443-3446

Normal cell polarity protects epithelial cells against Pseudomonas aeruginosa invasion and cytotoxicity. Using epithelial cell clones with selective defects in sorting of membrane constituents, and using hepatocyte growth factor pretreatment, we foun

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d5b54238bdb5ebfa1956ec2805f3df8c
https://doi.org/10.1128/iai.66.7.3443-3446.1998

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Conformational Changes of the Multidrug Transporter P-Glycoprotein in Solution and Lipid Discs

Autor: Maria-Elena Zoghbi, Leo Mok, Ina L. Urbatsch, Anukriti Singh, Greg Fendley, Guillermo A. Altenberg, Douglas J. Swartz

Publikováno v: Biophysical Journal. 110:229a

P-glycoprotein (Pgp) exports hundreds of chemically unrelated, hydrophobic compounds out of cells. Since Pgp can greatly affect bioavailability, pharmacokinetics and efficacy of therapeutic drugs, there is great interest in understanding the mechanis

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70a5456a5b2b07dbeaddb705349be1f6
https://doi.org/10.1016/j.bpj.2015.11.1264

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