Abstract:
:Structure-based design has gained credibility as a valuable component of the modern drug discovery process. The technique of SSNMR (solid-state NMR) promises to be a useful counterpart to the conventional experimental techniques of X-ray crystallography and solution-state NMR for providing structural features of drug targets that can guide medicinal chemistry towards drug candidates. This article highlights some recent SSNMR approaches from our group for identifying active compounds, such as enzyme inhibitors, receptor antagonists and peptide agents, that prevent the aggregation of amyloid proteins involved in neurodegenerative diseases. It is anticipated that the use of SSNMR in drug discovery will become more widespread in the wake of advances in hardware and methodological developments.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Middleton DAdoi
10.1042/BST0350985subject
Has Abstractpub_date
2007-11-01 00:00:00pages
985-90issue
Pt 5eissn
0300-5127issn
1470-8752pii
BST0350985journal_volume
35pub_type
杂志文章,评审abstract::Disrupted in schizophrenia 1 (DISC1) is emerging in the eyes of many as the most promising candidate of all the schizophrenia risk genes. This viewpoint is derived from the combination of genetic, clinical, imaging and rapidly advancing cell biology data around this gene. All of these areas have been reviewed extensiv...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0351283
更新日期:2007-11-01 00:00:00
abstract::Human heparan sulphate N-deacetylase/N-sulphotransferase 1 sulphates the NH(3) (+) group of the glucosamine moiety of the heparan chain in heparan sulphate/heparin biosynthesis. An open cleft that runs perpendicular to the sulphate donor 3'-phosphoadenosine 5'-phosphosulphate may constitute the acceptor substrate-bind...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310331
更新日期:2003-04-01 00:00:00
abstract::In this study the network of ATP-consuming and -producing reactions, interacting via the cytosolic ATP/ADP+P(i) system, was studied for the first time in an intact organ, the isolated perfused rat liver, using top-down metabolic-control analysis. Flux control in the metabolically resting state (only oxidative phosphor...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0280109
更新日期:2000-02-01 00:00:00
abstract::Recent studies of some proteins involved in the formation of focal adhesions are described. These include fibronectin, integrins, talin, Dok1 and filamin. Emphasis is placed on features that facilitate regulated assembly of complexes; these include a modular construction and flexible regions that provide interaction s...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0360263
更新日期:2008-04-01 00:00:00
abstract::After years of setbacks, the perspective of neuroprotective stroke therapy has revived in light of recent study results. We outline in this review how a neuroprotective candidate drug should be developed, beginning with a thorough preclinical evaluation according to the STAIR (Stroke Therapy Academic Industry Roundtab...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341271
更新日期:2006-12-01 00:00:00
abstract::BK (large conductance calcium- and voltage-activated potassium) channels are important determinants of physiological control in the nervous, endocrine and vascular systems with channel dysfunction associated with major disorders ranging from epilepsy to hypertension and obesity. Thus the mechanisms that control channe...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20120226
更新日期:2013-02-01 00:00:00
abstract::The binding sites of the oestrogen receptors alpha and beta have a structural requirement for ligands with two oxygen atoms (one of which is phenolic) spaced 11-12 A apart. They are open to many non-steroidal compounds, such as those from plants and the chemical industry. The importance of this interaction is the subj...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/0300-5127:0290231
更新日期:2001-05-01 00:00:00
abstract::Based on recent theoretical results on optimal flux distributions in kinetic metabolic networks, we explore the congruences and differences between solutions of kinetic optimization problems and results obtained by constraint-based methods. We demonstrate that, for a certain resource allocation problem, kinetic optimi...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150156
更新日期:2015-12-01 00:00:00
abstract::Protein aggregation is being found to be associated with an increasing number of human diseases. Aggregation can lead to a loss of function (lack of active protein) or to a toxic gain of function (cytotoxicity associated with protein aggregates). Although potentially harmful, protein sequences predisposed to aggregati...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120160
更新日期:2012-10-01 00:00:00
abstract::The expression of diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) with predicted molecular mass of 56.9. kDa (BnDGAT1) was examined using microspore-derived cell suspension cultures of oilseed rape (Brassica napus L. cv Jet Neuf). As well, a recombinant histidine-tagged N-terminal fragment of BnDGAT1 [BnDGAT1((1-11...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Findings from gene expression profiling studies are leading to new diagnostic and therapeutic strategies that can be applied in medical practice, especially in the field of oncology. Promising results of gene expression profiling of the peripheral blood in patients with ischaemic stroke have been obtained in recent pi...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341313
更新日期:2006-12-01 00:00:00
abstract::LRRK2 mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamaterg...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180468
更新日期:2018-12-17 00:00:00
abstract::CoA (coenzyme A) and its derivatives have a critical role in regulating cardiac energy metabolism. This includes a key role as a substrate and product in the energy metabolic pathways, as well as serving as an allosteric regulator of cardiac energy metabolism. In addition, the CoA ester malonyl-CoA has an important ro...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140094
更新日期:2014-08-01 00:00:00
abstract::Zebrafish (Danio rerio) are becoming an increasingly powerful model organism to study the role of metabolism in disease. Since its inception, the zebrafish model has relied on unique attributes such as the transparency of embryos, high fecundity and conservation with higher vertebrates, to perform phenotype-driven che...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180335
更新日期:2019-02-28 00:00:00
abstract::In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the beta- and gamma-secretases to release the Abeta (amyloid-beta) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved b...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330335
更新日期:2005-04-01 00:00:00
abstract::Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) and shingles (zoster). Although considered benign diseases, both varicella and zoster can cause complications. Zoster is painful and can lead to post herpetic neuralgia. VZV has also been linked to stroke, related to giant cell arteritis in...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190511
更新日期:2020-12-01 00:00:00
abstract::Recent progress in understanding the plant NE (nuclear envelope) has resulted from significant advances in identifying and characterizing the protein constituents of the membranes and nuclear pores. Here, we review recent findings on the membrane integral and membrane-associated proteins of the key domains of the NE, ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380307
更新日期:2010-02-01 00:00:00
abstract::The membranes of living cells have been shown to be highly organized into distinct microdomains, which has spatial and temporal consequences for the interaction of membrane bound receptors and their signalling partners as complexes. Fluorescence correlation spectroscopy (FCS) is a technique with single cell sensitivit...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150285
更新日期:2016-04-15 00:00:00
abstract::Glycosaminoglycans (GAGs), present in the extracellular matrix, are exploited by numerous, distinct microbes for cellular attachment, adhesion, invasion and evasion of the host immune system. Glycosaminoglycans, including the widely used, clinical anticoagulant heparin and semi-synthetic analogues thereof, have been r...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20170404
更新日期:2018-08-20 00:00:00
abstract::Plant chloroplasts contain an intricate photosynthetic membrane system, the thylakoids, and are surrounded by two envelope membranes at which thylakoid lipids are assembled. The glycoglycerolipids mono- and digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol as well as phosphatidylglycerol, are present in th...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110752
更新日期:2012-04-01 00:00:00
abstract::The driving force of the cell cycle is the activities of cyclin-dependent kinases (CDKs). Key steps in the regulation of the cell cycle therefore must impinge upon the activities of the CDKs. CDKs exert their functions when bound to cyclins that are expressed cyclically during the cell cycle. Polyamine biosynthesis va...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310366
更新日期:2003-04-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized countries. NAFLD develops in the absence of alcohol abuse and encompasses a wide spectrum of disorders ranging from benign fatty liver to non-alcoholic steatohepatitis (NASH). NASH often leads to fibrosis, cirrhosis a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140138
更新日期:2014-10-01 00:00:00
abstract::The energy-converting NADH:ubiquinone oxidoreductase, also known as respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of ions across the membrane. It was assumed that the complex exclusively works as a proton pump. Recently, it has been proposed that complex I from...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0330836
更新日期:2005-08-01 00:00:00
abstract::Large dense-core vesicles (LDCVs) were labelled in cultured bovine adrenal chromaffin cells expressing fluorescent chimaeric 'cargo' proteins that were targeted to these secretory vesicles. When the cells were stimulated with nicotine 48 h after transduction, the fractional loss of fluorescent LDCVs was much greater t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310851
更新日期:2003-08-01 00:00:00
abstract::During early flower development in Arabidopsis, floral stem cells proliferate and produce a sufficient amount of cells that are recruited for organogenesis. However, after the central organ primordia initiate, stem cell activity in the floral meristem is terminated to ensure the differentiation of a fixed number of fl...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380613
更新日期:2010-04-01 00:00:00
abstract::The SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) is probably the most extensively studied membrane protein transporter. There is a vast array of diverse inhibitors for the Ca2+ pump, and many have proved significant in helping to elucidate both the mechanism of transport and gaining conformational structures...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0390789
更新日期:2011-06-01 00:00:00
abstract::For a disease such as cancer, where a number of alterations to normal cell function accumulate over time, there are several opportunities to inhibit, slow down or even reverse the process. Many of the changes which drive the disease process occur in cell-signalling pathways that regulate proliferation and apoptosis. A...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0280007
更新日期:2000-02-01 00:00:00
abstract::Moonlighting proteins serve one or more novel functions in addition to their canonical roles. Moonlighting functions arise when an adventitious interaction between a protein and a new partner improves fitness of the organism. Selective pressure for improvement in the new function can result in two alternative outcomes...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140245
更新日期:2014-12-01 00:00:00
abstract::The IRF [IFN (interferon) regulatory factor] family of transcription factors control many cellular processes, including induction of key antiviral cytokines, type I IFNs, following viral infection. Recent studies have revealed several endogenous and viral proteins involved in ubiquitin-mediated regulation of IRF activ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0360453
更新日期:2008-06-01 00:00:00
abstract::Mouse ES (embryonic stem) cells maintain pluripotency with robust proliferation in vitro. ES cells share some similarities with cancer cells, such as anchorage-independent growth, loss of contact inhibition and tumour formation. After differentiation, ES cells lose pluripotency and tumorigenicity. Recent studies showe...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20051522
更新日期:2005-12-01 00:00:00