Abstract:
:Much work has gone into understanding the physical basis of the enormous catalytic power of enzymes over the last 50 years or so. Nevertheless, the detailed mechanism used by Nature's catalysts to speed chemical transformations remains elusive. DHFR (dihydrofolate reductase) has served as a paradigm to study the relationship between the structure, function and dynamics of enzymatic transformations. A complex reaction cascade, which involves rearrangements and movements of loops and domains of the enzyme, is used to orientate cofactor and substrate in a reactive configuration from which hydride is transferred by quantum mechanical tunnelling. In the present paper, we review results from experiments that probe the influence of protein dynamics on the chemical step of the reaction catalysed by TmDHFR (DHFR from Thermotoga maritima). This enzyme appears to have evolved an optimal structure that can maintain a catalytically competent conformation under extreme conditions.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Allemann RK,Evans RM,Loveridge EJdoi
10.1042/BST0370349subject
Has Abstractpub_date
2009-04-01 00:00:00pages
349-53issue
Pt 2eissn
0300-5127issn
1470-8752pii
BST0370349journal_volume
37pub_type
杂志文章,评审abstract::With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery i...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150236
更新日期:2016-04-15 00:00:00
abstract::Iron, copper and zinc are essential metals for cell metabolism. Plants have evolved different schemes to efficiently mobilize low-solubility nutrients such as metals from their environment and to transport them between organs. In this review we highlight the divergences and convergences of the iron, copper and zinc up...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0300766
更新日期:2002-08-01 00:00:00
abstract::PD (Parkinson's disease) is an aetiologically heterogeneous disorder characterized by a clinical phenotype consisting of resting tremor, rigidity and bradykinesia. Motor symptoms are associated with a progressive loss of dopaminergic neurons, with Lewy body inclusions within surviving neurons. Although heritability st...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330586
更新日期:2005-08-01 00:00:00
abstract::Targeting of protein kinases and phosphatases to the cytoskeleton enhances the regulation of many signalling events. Cytoskeletal signalling complexes facilitate this process by optimizing the relay of messages from membrane receptors to specific sites on the actin cytoskeleton. These signals influence fundamental cel...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310087
更新日期:2003-02-01 00:00:00
abstract::Horses and other equids are unusual in producing protein-rich sweat for thermoregulation, a major component of which is latherin, a highly surface-active, non-glycosylated protein that is a member of the PLUNC (palate, lung and nasal epithelium clone) family. Latherin produces a significant reduction in water surface ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0391017
更新日期:2011-08-01 00:00:00
abstract::Unr (upstream of N-ras) is a eukaryotic RNA-binding protein that has a number of roles in the post-transcriptional regulation of gene expression. Originally identified as an activator of internal initiation of picornavirus translation, it has since been shown to act as an activator and inhibitor of cellular translatio...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140271
更新日期:2015-06-01 00:00:00
abstract::Yeast cells rely on the SPS-sensing pathway to respond to extracellular amino acids. This nutrient-induced signal transduction pathway regulates gene expression by controlling the activity of two redundant transcription factors: Stp1 and Stp2. These factors are synthesized as latent cytoplasmic proteins with N-termina...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370242
更新日期:2009-02-01 00:00:00
abstract::NMDARs (N-methyl-D-aspartate receptors) are considered to be a target for the inhibitory actions of ethanol. While profound inhibition of both native and recombinant NMDARs can be observed following the application of high concentrations of ethanol the levels of inhibition seen with lower concentrations of ethanol are...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0371423
更新日期:2009-12-01 00:00:00
abstract::The Drosophila melanogaster flightless I protein and its homologues in higher eukaryotes (FliI) are conserved members of the gelsolin family of actin-binding proteins. Members of the gelsolin family generally contain three or six copies of a 125-amino-acid residue gelsolin-related repeating unit, and may contain addit...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320940
更新日期:2004-12-01 00:00:00
abstract::Intracellular cross-talk or synergism between receptors coupled negatively to adenylate cyclase via PTX-sensitive Gi-protein(s) and receptors coupled to phospholipase C via PTX-insensitive G-proteins is prevalent in a variety of cell types (see above) and may represent a universal mechanism for the modulation of phosp...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0211124
更新日期:1993-11-01 00:00:00
abstract::Muscles are responsible for generating the forces required for the movement of multicellular organisms. Microscopically, these forces arise as a consequence of motor proteins (myosin) pulling and sliding along actin filaments. Current knowledge states that the molecular forces between actin and myosin are linear in na...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320694
更新日期:2004-11-01 00:00:00
abstract::There is increasing recognition that numerous neurodegenerative conditions have the same underlying pathogenetic mechanism, namely a change in protein conformation, where the beta-sheet content is increased. In Alzheimer's disease, amyloid deposition in the form of neuritic plaques and congophilic angiopathy is driven...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0300574
更新日期:2002-08-01 00:00:00
abstract::TLR8 (Toll-like receptor 8) is activated by ssRNAs (single-stranded RNAs) and synthetic imidazoquinoline compounds that resemble purines and have immunostimulatory activity. TLR8 agonists are particularly effective at inducing Th1-polarizing responses from human monocytes and myeloid dendritic cells, with the magnitud...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0351485
更新日期:2007-12-01 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::The fission yeast Schizosaccharomyces pombe primarily detects glucose via a cAMP-signalling pathway. Components of this pathway include the Git3 G-protein-coupled receptor and a heterotrimeric G-protein, from which the Gpa2 Galpha subunit activates adenylate cyclase (Git2/Cyr1). Three additional proteins, Git1, Git7 a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330257
更新日期:2005-02-01 00:00:00
abstract::Effective stroke therapies require recanalization of occluded cerebral blood vessels; however, early reperfusion can cause BBB (blood-brain barrier) injury, leading to cerebral oedema and/or devastating brain haemorrhage. These complications of early reperfusion, which result from excess production of ROS (reactive ox...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0341366
更新日期:2006-12-01 00:00:00
abstract::Senescence is a tumour suppressor mechanism which is cell-intrinsically activated in the context of cellular stress. Senescence can further be propagated to neighbouring cells, a process called secondary senescence induction. Secondary senescence was initially shown as a paracrine response to the secretion of cytokine...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190109
更新日期:2020-06-30 00:00:00
abstract::The mTOR (mammalian target of rapamycin) signalling pathway functions as a nutrient sensor, both in individual cells and, more globally, in organs such as the fat body in Drosophila and the hypothalamus in the rat. The activity of placental amino acid transporters is decreased in IUGR (intrauterine growth restriction)...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370295
更新日期:2009-02-01 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::RNA pseudoknots are structural elements found in almost all classes of RNA. Pseudoknots form when a single-stranded region in the loop of a hairpin base-pairs with a stretch of complementary nucleotides elsewhere in the RNA chain. This simple folding strategy is capable of generating a large number of stable three-dim...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0360684
更新日期:2008-08-01 00:00:00
abstract::The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the 'hallmarks o...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110663
更新日期:2012-02-01 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::PGs (prostaglandins) are synthesized through the cyclo-oxygenase (COX-1 and -2) pathway in a variety of cells in response to various physiological stimuli. All cells require at least one pathway for apoptosis, and mitochondrial play a central role in regulation of apoptosis. In a previous study, incubation of A549 cel...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0321078
更新日期:2004-12-01 00:00:00
abstract::JNK (c-Jun N-terminal kinase) is a member of the MAPK (mitogen-activated protein kinase) family that regulates a range of biological processes implicated in tumorigenesis and neurodegenerative disorders. For example, genetic studies have demonstrated that the removal of specific Jnk genes can reduce neuronal death ass...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110641
更新日期:2012-02-01 00:00:00
abstract::The recruitment of the furanosidic scaffold of ribose as the crucial step for nucleotides and then for nucleic acids synthesis is presented. Based on the view that the selection of molecules to be used for relevant metabolic purposes must favor structurally well-defined molecules, the inadequacy of ribose as a prefere...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20190749
更新日期:2019-12-20 00:00:00
abstract::Lysophosphatidic acid (LPA; 1-acyl-3-phosphoglycerol) exerts its biological activity through both extracellular and intracellular targets. Receptor targets include the cell-surface G-protein-coupled receptors LPA(1-4) and the nuclear PPAR-gamma (peroxisome-proliferator-activated receptor gamma). Enzyme targets include...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20051366
更新日期:2005-12-01 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::We study how mechanical forces integrate spatially and temporally with regulatory signals at the leading edge of migrating cells. To probe the dynamics of this system, we developed quantitative fluorescent speckle microscopy, which maps out actin cytoskeleton transport, assembly and disassembly with high spatial resol...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20051250
更新日期:2005-12-01 00:00:00
abstract::The n-6 polyunsaturated fatty acid, arachidonic acid, is a precursor of prostaglandins, leukotrienes and related compounds that have important roles as mediators and regulators of inflammation. Consuming increased amounts of long chain n-3 polyunsaturated fatty acids (found in oily fish and fish oils) results in a par...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330423
更新日期:2005-04-01 00:00:00
abstract::Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegenerat...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380150
更新日期:2010-02-01 00:00:00