A single active catalytic site is sufficient to promote transport in P-glycoprotein (NDA@SZTAKI, Nemzeti Digitális Adattár, National Digital Data Archive)

A single active catalytic site is sufficient to promote transport in P-glycoprotein

Metaadatok

Tartalom:	http://real.mtak.hu/36200/
Archívum:	MTA Könyvtár
Gyûjtemény:	Status = Published Type = Article
Cím:	A single active catalytic site is sufficient to promote transport in P-glycoprotein
Létrehozó:	BÃ¡rsony, orsolya SzalÃ³ki, GÃ¡bor TÃ¼rk, DÃ³ra TarapcsÃ¡k, Szabolcs Gutay-TÃ³th, Zsuzsanna BacsÃ³, Zsolt SzÃ©kvÃ¶lgyi, LÃ³rÃ¡nt SzabÃ³, GÃ¡bor CsanÃ¡dy, LÃ¡szlÃ³ SzakÃ¡cs, Gergely KormosnÃ© Goda, Katalin
Kiadó:	Nature Publishing Group
Dátum:	2016
Téma:	QH3011 Biochemistry / biokÃ©mia QH3020 Biophysics / biofizika
Tartalmi leírás:	P-glycoprotein (Pgp) is an ABC transporter responsible for the ATP-dependent efflux of chemotherapeutic compounds from multidrug resistant cancer cells. Better understanding of the molecular mechanism of Pgp-mediated transport could promote rational drug design to circumvent multidrug resistance. By measuring drug binding affinity and reactivity to a conformation-sensitive antibody we show here that nucleotide binding drives Pgp from a high to a low substrate-affinity state and this switch coincides with the flip from the inward- to the outward-facing conformation. Furthermore, the outward-facing conformation survives ATP hydrolysis: the post-hydrolytic complex is stabilized by vanadate, and the slow recovery from this state requires two functional catalytic sites. The catalytically inactive double Walker A mutant is stabilized in a high substrate affinity inward-open conformation, but mutants with one intact catalytic center preserve their ability to hydrolyze ATP and to promote drug transport, suggesting that the two catalytic sites are randomly recruited for ATP hydrolysis.
Nyelv:	angol
Típus:	Article PeerReviewed info:eu-repo/semantics/article
Formátum:	text
Azonosító:	http://real.mtak.hu/36200/1/srep24810.pdf BÃ¡rsony, orsolya and SzalÃ³ki, GÃ¡bor and TÃ¼rk, DÃ³ra and TarapcsÃ¡k, Szabolcs and Gutay-TÃ³th, Zsuzsanna and BacsÃ³, Zsolt and SzÃ©kvÃ¶lgyi, LÃ³rÃ¡nt and SzabÃ³, GÃ¡bor and CsanÃ¡dy, LÃ¡szlÃ³ and SzakÃ¡cs, Gergely and KormosnÃ© Goda, Katalin (2016) A single active catalytic site is sufficient to promote transport in P-glycoprotein. SCIENTIFIC REPORTS, 6 (24810). pp. 1-16. ISSN 2045-2322
Kapcsolat:	http://real.mtak.hu/36200/ http://dx.doi.org/10.1038/srep24810 MTMT:3057146; doi:10.1038/srep24810