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51.
The vertebrate A-P axis is a time axis. The head is made first and more and more posterior levels are made at later and later stages. This is different to the situation in most other animals, for example, in Drosophila. Central to this timing is Hox temporal collinearity (see below). This occurs rarely in the animal kingdom but is characteristic of vertebrates and is used to generate the primary axial Hox pattern using time space translation and to integrate successive derived patterns (see below). This is thus a different situation than in Drosophila, where the primary pattern guiding Hox spatial collinearity is generated externally, by the gap and segmentation genes. 相似文献
52.
AJ Durston 《Current Genomics》2012,13(4):265-266
53.
Transmethylation, transsulfuration, and aminopropylation reactions of S-adenosyl-L-methionine in vivo 总被引:2,自引:0,他引:2
P Giulidori M Galli-Kienle E Catto G Stramentinoli 《The Journal of biological chemistry》1984,259(7):4205-4211
S-Adenosylmethionine (AdoMet) is metabolized through three main pathways, i.e. (a) transfer of its methyl group to a variety of methyl acceptors, (b) decarboxylation followed by aminopropylation leading to polyamine synthesis, and (c) cleavage of the bond between the sulfur atom and carbon 4 of the amino acid chain, resulting in formation of methylthioadenosine and homoserine thiolactone. In this study the metabolism of AdoMet through these pathways was studied after intravenous administration to rats of [1-14C]-, [3,4-14C]-, [methyl-14C]-, and [35S]AdoMet at various doses. The relative utilization of AdoMet and methionine was also investigated. The results show that intravenously administered AdoMet is efficiently metabolized in vivo up to the highest tested dose (250 mumol X kg-1 body weight), about two-thirds of the metabolized compound being utilized via transmethylation and cleavage to methylthioadenosine and one-third via decarboxylation. The efficient incorporation of the methyl group of AdoMet into muscle creatine indicates unambiguously that the compound is taken up and metabolized by the liver. Moreover, intravenously administered AdoMet is shown to be a better precursor than methionine both in creatine formation and in the utilization of the sulfur atom in transsulfuration reactions. 相似文献
54.
The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil
Conners R Hill DJ Borodina E Agnew C Daniell SJ Burton NM Sessions RB Clarke AR Catto LE Lammie D Wess T Brady RL Virji M 《The EMBO journal》2008,27(12):1779-1789
Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection. 相似文献
55.
Zaccheo OJ Prince SN Miller DM Williams C Kemp CF Brown J Jones EY Catto LE Crump MP Hassan AB 《Journal of molecular biology》2006,359(2):403-421
Ligands of the IGF-II/mannose 6-phosphate receptor (IGF2R) include IGF-II and mannose 6-phosphate modified proteins. Disruption of the negative regulatory effects of IGF2R on IGF-II-induced growth can lead to embryonic lethality and cancer promotion. Of the 15 IGF2R extracellular domains, domains 1-3 and 11 are known to have a conserved beta-barrel structure similar to that of avidin and the cation-dependent mannose 6-phosphate receptor, yet only domain 11 binds IGF-II with high specificity and affinity. In order to define the functional basis of this critical biological interaction, we performed alanine mutagenesis of structurally determined solvent-exposed loop residues of the IGF-II-binding site of human domain 11, expressed these mutant forms in Pichia pastoris, and determined binding kinetics with human IGF-II using isothermal calorimetry and surface plasmon resonance with transition state thermodynamics. Two hydrophobic residues in the CD loop (F1567 and I1572) were essential for binding, with a further non-hydrophobic residue (T1570) that slows the dissociation rate. Aside from alanine mutations of AB loop residues that decrease affinity by modifying dissociation rates (e.g. Y1542), a novel mutation (E1544A) of the AB loop enhanced affinity by threefold compared to wild-type. Conversion from an acidic to a basic residue at this site (E1544K) results in a sixfold enhancement of affinity via modification principally of the association rate, with enhanced salt-dependence, decreased entropic barrier and retained specificity. These data suggest that a functional hydrophobic binding site core is formed by I1572 and F1567 located in the CD loop, which initially anchors IGF-II. Within the AB loop, residues normally act to either stabilise or function as negative regulators of the interaction. These findings have implications for the molecular architecture and evolution of the domain 11 IGF-II-binding site, and the potential interactions with other domains of IGF2R. 相似文献
56.
Bernhard Y Renard Marc Kirchner Hanno Steen Judith AJ Steen Fred A Hamprecht 《BMC bioinformatics》2008,9(1):355
Background
The reliable extraction of features from mass spectra is a fundamental step in the automated analysis of proteomic mass spectrometry (MS) experiments. 相似文献57.
Christa Testerink Paul B Larsen Fionn McLoughlin Dieuwertje van der Does John AJ van Himbergen Teun Munnik 《Plant signaling & behavior》2008,3(9):681-683
Constitutive triple response 1 (CTR1) is a protein kinase that represses plant responses to ethylene. Recently, we have shown that CTR1 function is negatively regulated by the lipid second messenger phosphatidic acid (PA) in vitro.1 PA was shown to inhibit (1) CTR1''s protein kinase activity, (2) the intramolecular interaction between N-terminus and kinase domain, and (3) the interaction of CTR1 with the ethylene receptor ETR1. PA typically accumulates within minutes in response to biotic or abiotic stresses, which are known to induce ethylene formation. Although long-term treatment with ethephon does stimulate PA accumulation, our results show no fast increase in PA in response to ethylene. A speculative model is presented which explains how stress-induced PA formation could switch on downstream ethylene responses via interaction of the lipid with CTR1.Key words: lipid signaling, phosphatidic acid, ethylene, constitutive triple response 1, plant stress signaling, protein kinase, phospholipase D 相似文献
58.
Byeongyeon Park Ji Hye Nam Jin Han Kim Hyoung Ja Kim Valentina Onnis Gianfranco Balboni Kyung-Tae Lee Jeong Ho Park Marco Catto Angelo Carotti Jae Yeol Lee 《Bioorganic & medicinal chemistry letters》2017,27(5):1179-1185
A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and strong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC50 values of 45 nM and 62 nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of 3,4-dihydroquinazoline derivatives. As expected, compound 8b and 8d bind to both catalytic anionic site (CAS) and peripheral site (PS) of BChE with better interaction energy values than AChE, in agreement with our experimental data. Furthermore, the non-competitive/mixed-type inhibitions of both compounds further confirmed their dual binding nature in kinetic studies. 相似文献
59.
The utility of the morphological variation of pollen for resolving the evolutionary history of Billia (subfam. Hippocastanoideae,Sapindaceae)
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In this study, we examined the utility of pollen morphology for resolving questions about the evolutionary history of Billia, which is a poorly known genus of Neotropical trees. Billia has been traditionally circumscribed with two species and treated as sister to Aesculus L. However, the number of species in Billia is uncertain, because the genus exhibits abundant morphological diversity but little discontinuous variation. Therefore, Billia may be monotypic and highly polymorphic, or it may have two species with blurred boundaries due to incipient speciation and/or hybridization. Moreover, one recent molecular phylogenetic study shows Billia nested withinAesculus. Our work sought to address the following questions: (i) Are there discontinuities in the pollen of Billia that may suggest species boundaries? (ii) Does the pollen of Billia show evidence for inter-specific hybridization? (iii) Do the exine morphology and size of pollen in Billia differ from those in Aesculus? Our results from scanning electron microscopy showed that pollen exine morphology is not taxonomically informative in Billia but that there are significant differences in pollen size between red- and white-flowered individuals. Thus, our pollen data support the utility of flower color in Billia for species delimitation. Our assessments of pollen viability do not support hybridization in the genus, but cannot be used to rule it out. Finally, pollen exine morphology may lend some support to an evolutionary origin ofBillia within eastern North American Aesculus. In contrast, data on pollen size suggest that Billia may belong in a topological position outside of Aesculus. 相似文献
60.