Journal ArticleDOI
Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport.
Stephen C. Hyde,Paul Emsley,Michael J. Hartshorn,Michael M. Mimmack,Uzi Gileadi,Stephen R. Pearce,Stephen R. Pearce,Maurice P. Gallagher,Maurice P. Gallagher,Deborah R. Gill,Roderick E. Hubbard,Christopher F. Higgins +11 more
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TLDR
A tertiary structure model of the ATP-binding cassettes characteristic of this class of transport system is presented, based on similarities between the predicted secondary structures of members of this family and the previously determined structure of adenylate kinase.Abstract:
THE ATP-binding cassette (ABC) superfamily of transport systems now includes over thirty proteins that share extensive sequence similarity and domain organization (reviewed in refs 1–3). This superfamily includes the well characterized periplasmic binding protein-dependent uptake systems of prokaryotes, bacterial exporters, and eukaryotic proteins including the P-glycoprotein associated with multidrug resistance in tumours (MDR), the STE6 gene product that mediates export of yeast a-factor mating pheromone, pfMDR that is implicated in chloroquine resistance of the malarial parasite, and the product of the cystic fibrosis gene (CFTR). Here we present a tertiary structure model of the ATP-binding cassettes characteristic of this class of transport system, based on similarities between the predicted secondary structures of members of this family and the previously determined structure of adenylate kinase. This model has implications for both the molecular basis of transport and cystic fibrosis and provides a framework for further experimentation.read more
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Journal ArticleDOI
ABC Transporters: From Microorganisms to Man
TL;DR: This chapter discusses thebuilding blocks of the Transmembrane Complex, and some of the properties of these blocks have changed since the publication of the original manuscript in 1993.
Journal ArticleDOI
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
Susan P.C. Cole,Gabu Bhardwaj,James H. Gerlach,J. E. Mackie,Caroline E. Grant,Kurt C. Almquist,Alistair J. Stewart,Ebba U. Kurz,A. M. V. Duncan,Roger G. Deeley +9 more
TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Journal ArticleDOI
The human ATP-binding cassette (ABC) transporter superfamily
TL;DR: The ATP-binding cassette (ABC) transporters are essential for many processes in the cell and mutations in these genes cause or contribute to several human genetic disorders including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response.
Journal ArticleDOI
The Human ATP-Binding Cassette (ABC) Transporter Superfamily
TL;DR: The current knowledge of the human ABC genes, their role in inherited disease, and understanding of the topology of these genes within the membrane are reviewed.
Journal ArticleDOI
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis
Seng H. Cheng,Richard J. Gregory,John Marshall,Sucharita Paul,David W. Souza,Gary A. White,Catherine R. O'Riordan,Alan E. Smith +7 more
TL;DR: It is proposed that the mutant versions of CFTR are recognized as abnormal and remain incompletely processed in the endoplasmic reticulum where they are subsequently degraded.
References
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Journal ArticleDOI
CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
Bernard R. Brooks,Robert E. Bruccoleri,Barry D. Olafson,David J. States,S. Swaminathan,Martin Karplus +5 more
TL;DR: The CHARMM (Chemistry at Harvard Macromolecular Mechanics) as discussed by the authors is a computer program that uses empirical energy functions to model macromolescular systems, and it can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations.
Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Journal ArticleDOI
Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
TL;DR: Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.
Journal ArticleDOI
The biochemistry of P-glycoprotein-mediated multidrug resistance.
Jane A. Endicott,Ling +1 more
Journal ArticleDOI
Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins
TL;DR: The complete nucleotide and primary structure of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented and strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide.