Abstract:
:As beta-secretase, memapsin 2 cleaves amyloid-beta precursor protein, which leads ultimately to the onset of Alzheimer's disease. As such, memapsin 2 is an excellent target of inhibitor drugs for the treatment of this disease. Here we describe the tools for memapsin 2 inhibitor design that have been developed and results from the structure-based inhibitor design. Strategy for the design of memapsin 2 inhibitors with pharmaceutical potential is also discussed.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Hong L,Turner RT 3rd,Koelsch G,Ghosh AK,Tang Jdoi
10.1042/bst0300530keywords:
subject
Has Abstractpub_date
2002-08-01 00:00:00pages
530-4issue
4eissn
0300-5127issn
1470-8752journal_volume
30pub_type
杂志文章,评审abstract::Growing evidence supports the view that LDs (lipid droplets) are dynamic organelles that can serve both as an intracellular signalling compartment and as an organizing platform orchestrating many vital processes in eukaryotic cells. It has become clear that the LDs-confined deposition and lipolytic degradation of neut...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0371050
更新日期:2009-10-01 00:00:00
abstract::UBDs [Ub (ubiquitin)-binding domains], which are typically small protein motifs of <50 residues, are used by receptor proteins to transduce post-translational Ub modifications in a wide range of biological processes, including NF-κB (nuclear factor κB) signalling and proteasomal degradation pathways. More than 20 fami...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110729
更新日期:2012-04-01 00:00:00
abstract::Post-translational modification (PTM) of histones has been investigated in eukaryotes for years, revealing its widespread occurrence and functional importance. Many PTMs affect chromatin folding and gene activity. Only recently the occurrence of such modifications has been recognized in bacteria. However, it is unclea...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180488
更新日期:2018-10-19 00:00:00
abstract::Luteinizing hormone (LH) interacts with its plasma membrane receptor to activate the formation of cyclic AMP via the regulatory GTP binding protein (Gs). This is followed by a desensitization of that same hormonal response which is caused by an uncoupling of the LH receptor from Gs. The coupling between Gs and the ade...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0170633
更新日期:1989-08-01 00:00:00
abstract::Nucleosomes are actively positioned along DNA by ATP-dependent, chromatin remodelling factors. A structural model for the ISW1a chromatin remodelling factor from Saccharomyces cerevisiae in complex with a dinucleosome substrate was constructed from the X-ray structures of ISW1a (ΔATPase) with and without DNA bound, tw...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20110748
更新日期:2012-04-01 00:00:00
abstract::Endocytosis of transmembrane receptors largely occurs via clathrin-coated vesicles that bud from the plasma membrane and deliver their cargo to the endosomal system for recycling or degradation. PIs (phosphoinositides) control the timing and localization of endocytic membrane trafficking by recruiting adaptors and oth...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20051285
更新日期:2005-12-01 00:00:00
abstract::Blood vessel formation during vertebrate development relies on a process called angiogenesis and is essential for organ growth and tissue viability. In addition, angiogenesis leads to pathological blood vessel growth in diseases with tissue ischaemia, such as neovascular eye disease and cancer. Neuropilin 1 (NRP1) is ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140244
更新日期:2014-12-01 00:00:00
abstract::The mRNA coding for FGF-2 (fibroblast growth factor 2), a major angiogenic factor, is translated by an IRES (internal ribosome entry site)-dependent mechanism. We have studied the role of the IRES in the regulation of FGF-2 expression in vivo, under pathophysiological conditions, by creating transgenic mice lines expr...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20060017
更新日期:2006-02-01 00:00:00
abstract::Rapid interphase chromosome territory repositioning appears to function through the action of nuclear myosin and actin, in a nuclear motor complex. We have found that chromosome repositioning when cells leave the cell cycle is not apparent in cells that have mutant lamin A or that are lacking emerin. We discuss the po...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0361384
更新日期:2008-12-01 00:00:00
abstract::PilZ domain-containing proteins constitute a large family of bacterial signaling proteins. As a widely distributed protein domain for the binding of the second messenger c-di-GMP, the canonical PilZ domain contains a set of motifs that define the binding site for c-di-GMP and an allosteric switch for propagating local...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180543
更新日期:2019-02-28 00:00:00
abstract::Cultured pluripotent stem cells hold great promise for regenerative medicine. Considerable efforts have been invested into the refinement and definition of improved culture systems that sustain self-renewal and avoid differentiation of pluripotent cells in vitro. Recent studies have, however, found that the choice of ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130049
更新日期:2013-06-01 00:00:00
abstract::The spliceosome is a macromolecular machine that carries out the excision of introns from eukaryotic pre-mRNAs and splicing together of exons. Four large RNA-protein complexes, called the U1, U2, U4/U6 and U5 small nuclear ribonucleoprotein particles (snRNPs), and some non-snRNP proteins assemble around three short co...
journal_title:Biochemical Society transactions
pub_type:
doi:10.1042/0300-5127:0290015
更新日期:2001-05-01 00:00:00
abstract::LRRK2 (leucine-rich repeat kinase 2) is an enzyme implicated in human disease, containing kinase and GTPase functions within the same multidomain open reading frame. Dominant mutations in the LRRK2 gene are the most common cause of familial PD (Parkinson's disease). Additionally, in genome-wide association studies, th...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120126
更新日期:2012-10-01 00:00:00
abstract::Colicins are protein antibiotics produced by Escherichia coli to kill closely related non-identical competing species. They have taken advantage of the promiscuity of several proteins in the cell envelope for entry into the bacterial cell. The Tol-Pal system comprises one such ensemble of periplasmic and membrane-asso...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120239
更新日期:2012-12-01 00:00:00
abstract::The glutamate/aspartate transporter GLAST-1 is expressed in bone in vivo and also exists as a splice variant (GLAST-1a) in which exon 3 is excluded. Since GLAST-1 expression is regulated in bone in response to osteogenic mechanical stimuli in vivo and binding of glutamate to receptors on osteoblasts increases osteobla...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0300890
更新日期:2002-11-01 00:00:00
abstract::Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140034
更新日期:2014-08-01 00:00:00
abstract::Ligand-gated ion channels function as rapid signal transducers, converting chemical signals (in the form of neurotransmitters) into electrical signals in the postsynaptic neuron. This is achieved by the recognition of neurotransmitter at its specific-binding sites, which then triggers the opening of an ion channel ('g...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320540
更新日期:2004-06-01 00:00:00
abstract::Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiol...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380498
更新日期:2010-04-01 00:00:00
abstract::Polycomb group (PcG) proteins are highly conserved chromatin-modifying complexes that implement gene silencing in higher eukaryotes. Thousands of genes and multiple developmental processes are regulated by PcG proteins. As the first chromatin modifier been identified in model plant Arabidopsis thaliana, the methyltran...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20200192
更新日期:2020-08-28 00:00:00
abstract::Tandem repeats (TR) in proteins are common in nature and have several unique functions. They come in various forms that are frequently difficult to recognize from a sequence. A previously proposed structural classification has been recently implemented in the RepeatsDB database. This defines five main classes, mainly ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150079
更新日期:2015-10-01 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::Nitrogenase activity in Rhodospirillum rubrum is post-translationally regulated by DRAG (dinitrogenase reductase glycohydrolase) and DRAT (dinitrogenase reductase ADP-ribosylation transferase). When a sudden increase in fixed nitrogen concentration or energy depletion is sensed by the cells, DRAG is inactivated and DR...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0340160
更新日期:2006-02-01 00:00:00
abstract::Trim25 is a member of the tripartite motif family of E3 ubiquitin ligases. It plays major roles in innate immunity and defence against viral infection, control of cell proliferation and migration of cancer cells. Recent work identified Trim25 as being able to bind to RNA and to regulate Lin28a-mediated uridylation of ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160077
更新日期:2016-08-15 00:00:00
abstract::The giant cytoskeletal kinases of the titin-like family are emerging as key mediators of stretch-sensing in muscle. It is thought that their elastic conformational deformation during muscle function regulates both their catalysis and the recruitment of regulatory proteins to signalosomes that assemble in their vicinit...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130085
更新日期:2013-08-01 00:00:00
abstract::In the present article, I discuss recent developments in the naming of the TOR (target of rapamycin) protein. In particular, I address the issue of mammalian target of rapamycin (mTOR) versus the newer mechanistic target of rapamycin (MTOR). mTOR is the name given by the TOR community almost two decades ago and widely...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20130092
更新日期:2013-08-01 00:00:00
abstract::The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made fr...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160125
更新日期:2016-10-15 00:00:00
abstract::Using the hyperthermophile Pyrococcus furiosus, we have delineated several key steps in CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) invader defence pathways. P. furiosus has seven transcriptionally active CRISPR loci that together encode a total of 200 crRNAs (CRISPR RNAs...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130056
更新日期:2013-12-01 00:00:00
abstract::The 26S proteasome is a non-lysosomal protease in the cytosol and nucleus of eukaryotic cells. Its main function is to mediate ubiquitin-dependent proteolysis. The 26S proteasome is a multimeric complex composed by the 20S proteasome CP (core particle) and the 19S RPs (regulatory particles). Although the atomic struct...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0380029
更新日期:2010-02-01 00:00:00
abstract::Smoking is the main risk factor for COPD (chronic obstructive pulmonary disease) but genetic factors are of importance, since only a subset of smokers develops the disease. Sex differences have been suggested both in disease prevalence and response to environmental exposures. Furthermore, it has been shown that acquis...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370814
更新日期:2009-08-01 00:00:00
abstract::Here, I review three new structural studies from our laboratory. First, the crystal structure of RNA polymerase (Pol) II in complex with an RNA inhibitor revealed that this RNA blocks transcription initiation by preventing DNA loading into the active-centre cleft. Secondly, the structure of the SRI (Set2 Rpb1-interact...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341058
更新日期:2006-12-01 00:00:00