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61.
Teall M Oakley P Harrison T Shaw D Kay E Elliott J Gerhard U Castro JL Shearman M Ball RG Tsou NN 《Bioorganic & medicinal chemistry letters》2005,15(10):2685-2688
The development of a novel series of 4-aryl, 4-phenylsulfonyl cyclohexananone-derived gamma-secretase inhibitors for the potential treatment of Alzheimer's disease is described. 相似文献
62.
Three-dimensional structure of (1,4)-beta-D-mannan mannanohydrolase from tomato fruit 总被引:2,自引:0,他引:2
Bourgault R Oakley AJ Bewley JD Wilce MC 《Protein science : a publication of the Protein Society》2005,14(5):1233-1241
The three-dimensional crystal structure of tomato (Lycopersicon esculentum) beta-mannanase 4a (LeMAN4a) has been determined to 1.5 A resolution. The enzyme adopts the (beta/alpha)(8) fold common to the members of glycohydrolase family GH5. The structure is comparable with those of the homologous Trichoderma reesei and Thermomonospora fusca beta-mannanases: There is a conserved three-stranded beta-sheet located near the N terminus that stacks against the central beta-barrel at the end opposite the active site. Three noncanonical beta-helices surround the active site. Similar helices are found in T. reesei but not T. fusca beta-mannanase. By analogy with other beta-mannanases, the catalytic acid/base residue is E204 and the nucleophile residue is E318. The active site cleft of L. esculentum beta-mannanase most closely resembles that of the T. reesei isozyme. A model of substrate binding in LeMAN4a is proposed in which the mannosyl residue occupying the -1 subsite of the enzyme adopts the (1)S(5) skew-boat conformation. 相似文献
63.
Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential 总被引:13,自引:0,他引:13
Bogoyevitch MA Boehm I Oakley A Ketterman AJ Barr RK 《Biochimica et biophysica acta》2004,1697(1-2):89-101
64.
65.
BJÖRN ROGELL MARTIN EKLUND HANNA THÖRNGREN ANSSI LAURILA JACOB HÖGLUND 《Molecular ecology》2010,19(11):2229-2240
Although loss of genetic variation is frequently assumed to be associated with loss of adaptive potential, only few studies have examined adaptation in populations with little genetic variation. On the Swedish west coast, the northern fringe populations of the natterjack toad Bufo calamita inhabit an atypical habitat consisting of offshore rock islands. There are strong among‐population differences in the amount of neutral genetic variation, making this system suitable for studies on mechanisms of trait divergence along a gradient of within‐population genetic variation. In this study, we examined the mechanisms of population divergence using QST–FST comparisons and correlations between quantitative and neutral genetic variation. Our results suggest drift or weak stabilizing selection across the six populations included in this study, as indicated by low QST–FST values, lack of significant population × temperature interactions and lack of significant differences among the islands in breeding pond size. The six populations included in this study differed in both neutral and quantitative genetic variation. Also, the correlations between neutral and quantitative genetic variation tended to be positive, however, the relatively small number of populations prevents any strong conclusions based on these correlations. Contrary to the majority of QST–FST comparisons, our results suggest drift or weak stabilizing selection across the examined populations. Furthermore, the low heritability of fitness‐related traits may limit evolutionary responses in some of the populations. 相似文献
66.
Aaron J. Oakley Marjorie Coggan Philip G. Board 《The Journal of biological chemistry》2010,285(13):9642-9648
γ-Glutamylamine cyclotransferase (GGACT) is an enzyme that converts γ-glutamylamines to free amines and 5-oxoproline. GGACT shows high activity toward γ-glutamyl-ϵ-lysine, derived from the breakdown of fibrin and other proteins cross-linked by transglutaminases. The enzyme adopts the newly identified cyclotransferase fold, observed in γ-glutamylcyclotransferase (GGCT), an enzyme with activity toward γ-glutamyl-α-amino acids (Oakley, A. J., Yamada, T., Liu, D., Coggan, M., Clark, A. G., and Board, P. G. (2008) J. Biol. Chem. 283, 22031–22042). Despite the absence of significant sequence identity, several residues are conserved in the active sites of GGCT and GGACT, including a putative catalytic acid/base residue (GGACT Glu82). The structure of GGACT in complex with the reaction product 5-oxoproline provides evidence for a common catalytic mechanism in both enzymes. The proposed mechanism, combined with the three-dimensional structures, also explains the different substrate specificities of these enzymes. Despite significant sequence divergence, there are at least three subfamilies in prokaryotes and eukaryotes that have conserved the GGCT fold and GGCT enzymatic activity. 相似文献
67.
Homograft or allograft tissue has been available for use as replacement for diseased valves or reconstruction of major vessels for decades. However, with respect to replacement of diseased valvular tissue the search for the ideal valve still continues. In this review we will discuss the clinical indications, surgical techniques, and outcome of aortic homografts. 相似文献
68.
During chromosome synthesis in Escherichia coli, replication forks are blocked by Tus bound Ter sites on approach from one direction but not the other. To study the basis of this polarity, we measured the rates of dissociation of Tus from forked TerB oligonucleotides, such as would be produced by the replicative DnaB helicase at both the fork-blocking (nonpermissive) and permissive ends of the Ter site. Strand separation of a few nucleotides at the permissive end was sufficient to force rapid dissociation of Tus to allow fork progression. In contrast, strand separation extending to and including the strictly conserved G-C(6) base pair at the nonpermissive end led to formation of a stable locked complex. Lock formation specifically requires the cytosine residue, C(6). The crystal structure of the locked complex showed that C(6) moves 14 A from its normal position to bind in a cytosine-specific pocket on the surface of Tus. 相似文献
69.
Diversity and Distribution of Planctomycetes and Related Bacteria in the Suboxic Zone of the Black Sea 总被引:2,自引:1,他引:1 下载免费PDF全文
John Kirkpatrick Brian Oakley Clara Fuchsman Sujatha Srinivasan James T. Staley James W. Murray 《Applied microbiology》2006,72(4):3079-3083
Samples from six depths of the Black Sea's suboxic zone were analyzed for 16S rRNA gene sequence information. A gradient in phylotype diversity was found. The distributions of known anaerobic ammonium oxidation (anammox) bacteria, many unknown Planctomycetes, and other phylotypes were examined in relation to the local nutrient and redox conditions. 相似文献
70.
A reductionist ecological approach of using a model genus was adopted in order to understand how microbial community structure is driven by metabolic properties. The distribution along an estuarine gradient of the highly specialised genus Methanosaeta was investigated and compared to the previously determined distribution of the more metabolically flexible Desulfobulbus. Methanosaeta genotypic distribution along the Colne estuary (Essex, UK) was determined by DNA- and RNA-based denaturing gradient gel electrophoresis and 16S rRNA gene sequence analyses. Methanosaeta distribution was monotonic, with a consistently diverse community and no apparent niche partitioning either in DNA or RNA analyses. This distribution pattern contrasts markedly with the previously described niche partitioning and sympatric differentiation of the model generalist, Desulfobulbus. To explain this difference, it is hypothesised that Methanosaeta's strict metabolic needs limit its adaptation potential, thus populations do not partition into spatially distinct groups and so do not appear to be constrained by gross environmental factors such as salinity. Thus, at least for these two model genera, it appears that metabolic flexibility may be an important factor in spatial distribution and this may be applicable to other microbes. 相似文献