Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues.
One of the Holy Grails of ATP-binding cassette transporter research is a structural understanding of drug binding and transport in a eukaryotic multidrug resistance pump. These transporters are front-line mediators of drug resistance in cancers and represent an important therapeutic target in future chemotherapy. Although there has been intensive biochemical research into the human multidrug pumps, their 3D structure at atomic resolution remains unknown. The recent determination of the structure of a mouse P-glycoprotein at subatomic resolution is complemented by structures for a number of prokaryotic homologues. These structures have provided advances into our knowledge of the ATP-binding cassette exporter structure and mechanism, and have provided the template data for a number of homology modelling studies designed to reconcile biochemical data on these clinically important proteins.
Kerr
Ian D
ID
School of Biomedical Sciences, University of Nottingham, Nottingham, UK. Ian.kerr@nottingham.ac.uk
Jones
Peter M
PM
George
Anthony M
AM
D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C079726:MsbA protein, Bacteria; C421109:multidrug resistance-associated protein 1