Abstract:
:Membrane proteins are intrinsically involved in both human and pathogen physiology, and are the target of 60% of all marketed drugs. During the past decade, advances in the studies of membrane proteins using X-ray crystallography, electron microscopy and NMR-based techniques led to the elucidation of over 250 unique membrane protein crystal structures. The aim of the European Drug Initiative for Channels and Transporter (EDICT) project is to use the structures of clinically significant membrane proteins for the development of lead molecules. One of the approaches used to achieve this is a virtual high-throughput screening (vHTS) technique initially developed for soluble proteins. This paper describes application of this technique to the discovery of inhibitors of the leucine transporter (LeuT), a member of the neurotransmitter:sodium symporter (NSS) family.
journal_name
Mol Membr Bioljournal_title
Molecular membrane biologyauthors
Simmons KJ,Gotfryd K,Billesbølle CB,Loland CJ,Gether U,Fishwick CW,Johnson APdoi
10.3109/09687688.2012.710341subject
Has Abstractpub_date
2013-03-01 00:00:00pages
184-94issue
2eissn
0968-7688issn
1464-5203journal_volume
30pub_type
杂志文章abstract::This investigation is aimed at defining the structural requirements for aliphatic polyamines to interact with mitochondrial binding sites, which are relevant for the regulation of the permeability transition and for mitochondrial polyamine uptake. The triamines N-aminoethyl-1,2-diaminoethane (dien) and N-aminopropyl-1...
journal_title:Molecular membrane biology
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doi:10.1080/09687680310001654916
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journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
pub_type: 杂志文章,评审
doi:10.3109/09687688.2010.521201
更新日期:2010-11-01 00:00:00
abstract::The effect of cholesterol and lanosterol on the formation of structures in the gel/subgel phase of 1,2-dipalmitoylphosphatidylcholine was investigated using freeze-fracture electron microscopy and X-ray diffraction. Mixtures with up to 25 mol% sterol were analysed after annealing for between several days and some mont...
journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
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journal_title:Molecular membrane biology
pub_type: 杂志文章,评审
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abstract::Membrane microdomains enriched in cholesterol, sphingolipids (rafts), and specific proteins are involved in important physiological functions. However their structure, size and stability are still controversial. Given that detergent-resistant membranes (DRMs) are in the liquid-ordered state and are rich in raft-like c...
journal_title:Molecular membrane biology
pub_type: 杂志文章
doi:10.3109/09687688.2014.949319
更新日期:2014-09-01 00:00:00
abstract::TGN38 is a heavily glycosylated, type I integral membrane protein which is predominantly localized to the trans Golgi network (TGN), but which constitutively traffics between the TGN and the cell surface. The trafficking of TGN38 has been extensively studied in non-polarized cells, and a short, tyrosine-based, peptide...
journal_title:Molecular membrane biology
pub_type: 杂志文章
doi:10.3109/09687689809074524
更新日期:1998-07-01 00:00:00
abstract::Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This rep...
journal_title:Molecular membrane biology
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::The cyanelles of the glaucocystophyte alga Cyanophora paradoxa resemble endosymbiotic cyanobacteria in morphology, pigmentation and, especially, in the presence of a peptidoglycan wall situated between the inner and outer envelope membranes. However, it is now clear that cyanelles in fact are primitive plastids. Phylo...
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doi:10.1080/09687860500041411
更新日期:2005-01-01 00:00:00
abstract::The transverse distribution of phosphatidylglycerol (PG) across the inner membrane of Escherichia coli was studied. The oxidation of PG by periodate was used to discriminate between the PG present in the cytoplasmic and in the periplasmic leaflet of the inner membrane. Applied to large unilamellar vesicles derived of ...
journal_title:Molecular membrane biology
pub_type: 杂志文章
doi:10.3109/09687689709048168
更新日期:1997-01-01 00:00:00
abstract::Previous work from our laboratory has established bovine hippocampal membranes as a convenient natural source for studying neuronal receptors such as the G-protein coupled serotonin1A receptor. In this paper, we have explored the organization and dynamics of bovine hippocampal membranes using environment-sensitive and...
journal_title:Molecular membrane biology
pub_type: 杂志文章
doi:10.1080/09687860600803223
更新日期:2006-09-01 00:00:00
abstract::The transporter SbtA is a high affinity Na+-dependent HCO3- uptake system present in a majority of cyanobacterial clades. It functions in conjunction with CO2 uptake systems and other HCO3- uptake systems to allow cyanobacteria to accumulate high levels of HCO3- used to support efficient photosynthetic CO2 fixation vi...
journal_title:Molecular membrane biology
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doi:10.3109/09687688.2011.593049
更新日期:2011-08-01 00:00:00
abstract::Lipid rafts are specialized plasma membrane microdomains in which glycosphingolipids and cholesterol are major structural components. Their relative insolubility to nonionic detergents is the most widely used method to purify these structures. Several signalling proteins are associated with these microdomains in T lym...
journal_title:Molecular membrane biology
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abstract::Membrane proteins are ubiquitous in biology and are key targets for therapeutic development. Despite this, our structural understanding has lagged behind that of their soluble counterparts. This review provides an overview of this important field, focusing in particular on the recent resurgence of electron microscopy ...
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journal_title:Molecular membrane biology
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更新日期:1994-01-01 00:00:00
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journal_title:Molecular membrane biology
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doi:10.3109/09687689409162234
更新日期:1994-07-01 00:00:00
abstract::In hair cells of the inner ear, phosphatidylserine (PS), detected with fluorescent annexin V labeling, was rapidly exposed on the external leaflet of apical plasma membranes upon dissection of the organ of Corti. PS externalization was unchanged by caspase inhibition, suggesting that externalization did not portend ap...
journal_title:Molecular membrane biology
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更新日期:2007-01-01 00:00:00
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journal_title:Molecular membrane biology
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doi:10.1080/0968768021000035078
更新日期:2002-10-01 00:00:00
abstract::Calpain, an intracellular calcium-dependent protease, is activated at cell membranes and cleaves cytoskeletal and submembranous proteins. Calpain is inferred to be a calcium-dependent regulator for cytoskeletal reorganization. Calpastatin, an endogenous calpain inhibitor, inhibits not only the proteolytic activity of ...
journal_title:Molecular membrane biology
pub_type: 杂志文章,评审
doi:10.3109/09687689609160599
更新日期:1996-10-01 00:00:00
abstract::Insolubility of membrane components in non-ionic detergents such as Triton X-100 at low temperature is a widely used biochemical criterion to identify, isolate and characterize membrane domains. In this work, we monitored the detergent insolubility of the serotonin(1A) receptor in CHO cell membranes and its modulation...
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abstract::Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse bl...
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journal_title:Molecular membrane biology
pub_type: 杂志文章,评审
doi:10.3109/09687689509038489
更新日期:1995-01-01 00:00:00