ATP hydrolysis cycles and mechanism in P-glycoprotein and CFTR.
P-glycoprotein and CFTR are prominent members of the ABC Transporter family. Both use ATP, the former to drive extrusion of drugs from cells and confer multidrug-resistance, the latter to drive opening and closing of anion channels. We compare current working models of catalytic cycle and mechanism of the two proteins. In Pgp the NBDs appear functionally equivalent, in CFTR they appear functionally distinct. In both proteins, ATP hydrolysis occurs in both NBDs, and it is proposed that the two NBDs alternate in catalysis. Other differences and similarities are noted, fostering ideas for future developments.
Senior
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AE
Department of Biochemistry and Biophysics, University of Rochester Medical Center, NY, USA.
Gadsby
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DC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D006868:Hydrolysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate