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21.
Stephanie S. Schweiker Wendy A. Loughlin Christopher L. Brown Gregory K. Pierens 《Journal of peptide science》2009,15(6):442-450
The first solution state structural analysis (NMR) of the C‐terminal sequence of human GL that binds to glycogen phosphorylase a (GPa), PEWPSYLGYEKLGPYY‐NH2 ( 1 ), showed it to be in a random coil conformation. This was supported by molecular dynamics simulation (modelled in solution) using NAMD 2.6. The conformational ambiguity of the peptide makes the structural arrangement of the peptide (and internal residues) strongly dependent on the environment. Thirteen tetra‐peptide fragments of the C‐terminal sequence, YEKLG‐NH2, and the corresponding tri‐ and di‐peptide sequences were used in a fragment screen against GPa. Compound 2 (H‐GPYY‐NH2) did not give an IC50 value, whereas PEWPSYLGYEKLGPYY‐NH2 ( 1 ) displayed an IC50 of 34 µM against GPa. Truncated peptides derived from 1 , (EKL‐NH2, EKLG‐NH2, and AcEKNH2) inhibited GPa (21%, 32%, 63%, respectively at 22 mM ). These studies suggest key residues within the peptide chain have additional molecular interactions with GPa. The interaction of intra‐sequence residues in combination with the terminal residues of PEWPSYLGYEKLGPYY with GPa may form the basis for the design of new inhibitors of GPa. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
22.
Bipolar spindles must separate chromosomes by the appropriate distance during cell division, but mechanisms determining spindle length are poorly understood. Based on a 2D model of meiotic spindle assembly, we predicted that higher localized microtubule (MT) depolymerization rates could generate the shorter spindles observed in egg extracts of X. tropicalis compared to X. laevis. We found that katanin-dependent MT severing was increased in X. tropicalis, which, unlike X. laevis, lacks an inhibitory phosphorylation site in the katanin p60 catalytic subunit. Katanin inhibition lengthened spindles in both species. In X. tropicalis, k-fiber MT bundles that connect to chromosomes at their kinetochores extended through spindle poles, disrupting them. In both X. tropicalis extracts and the spindle simulation, a balance between k-fiber number and MT depolymerization is required to maintain spindle morphology. Thus, mechanisms have evolved in different species to scale spindle size and coordinate regulation of multiple MT populations in order to generate a robust steady-state structure. 相似文献
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Nuclear gene trees and the phylogenetic relationships of the mangabeys (Primates: Papionini) 总被引:2,自引:1,他引:2
Phylogenetic relationships of mangabeys within the Old World monkey tribe
Papionini are inferred from analyses of nuclear DNA sequences from five
unlinked loci. The following conclusions are strongly supported, based on
congruence among trees derived for the five separate gene regions: (1)
mangabeys are polyphyletic within the Papionini; (2) Cercocebus is the
sister taxon to the genus Mandrillus; and (3) Lophocebus belongs to a clade
with Papio and Theropithecus, with Papio as its most likely sister taxon.
Morphologically based phylogenies positing mangabey monophyly were
evaluated by mapping the sequences for each locus on these trees. The data
seem to fit these trees poorly in both maximum-parsimony and likelihood
analyses. Incongruence among nuclear gene trees occurred in the
interrelationships among Lophocebus, Papio, and Theropithecus. Several
factors that may account for this incongruence are discussed, including
sampling error, random lineage sorting, and introgression.
相似文献
25.
Differential allelic expression of the type II collagen gene (COL2A1) in osteoarthritic cartilage. 总被引:2,自引:0,他引:2 下载免费PDF全文
J Loughlin C Irven N Athanasou A Carr B Sykes 《American journal of human genetics》1995,56(5):1186-1193
Osteoarthritis (OA) is a common debilitating disease resulting from the degeneration of articular cartilage. The major protein of cartilage is type II collagen, which is encoded by the COL2A1 gene. Mutations at this locus have been discovered in several individuals with inherited disorders of cartilage. We have identified 27 primary OA patients who are heterozygous for sequence dimorphisms located in the coding region of COL2A1. These dimorphisms were used to distinguish the mRNA output from each of the two COL2A1 alleles in articular cartilage obtained from each patient. Three patients demonstrated differential allelic expression and produced < 12% of the normal level of mRNA from one of their COL2A1 alleles. The same allele shows reduced expression in all three patients, and this allele is more frequent in a well-defined OA population than in a control group, suggesting the possible existence of a rare COL2A1 allele that predisposes to OA. 相似文献
26.
Aims: The aim of this study was to compare both the antimicrobial activity of terpinen‐4‐ol and tea tree oil (TTO) against clinical skin isolates of meticillin‐resistant Staphylococcus aureus (MRSA) and coagulase‐negative staphylococci (CoNS) and their toxicity against human fibroblast cells. Methods and Results: Antimicrobial activity was compared by using broth microdilution and quantitative in vitro time‐kill test methods. Terpinen‐4‐ol exhibited significantly greater bacteriostatic and bactericidal activity, as measured by minimum inhibitory and bactericidal concentrations, respectively, than TTO against both MRSA and CoNS isolates. Although not statistically significant, time‐kill studies also clearly showed that terpinen‐4‐ol exhibited greater antimicrobial activity than TTO. Comparison of the toxicity of terpinen‐4‐ol and TTO against human fibroblasts revealed that neither agent, at the concentrations tested, were toxic over the 24‐h test period. Conclusions: Terpinen‐4‐ol is a more potent antibacterial agent against MRSA and CoNS isolates than TTO with neither agent exhibiting toxicity to fibroblast cells at the concentrations tested. Significance and Impact of the Study: Terpinen‐4‐ol should be considered for inclusion as a single agent in products formulated for topical treatment of MRSA infection. However, further work would initially be required to ensure that resistance would not develop with the use of terpinen‐4‐ol as a single agent. 相似文献
27.
The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice 下载免费PDF全文
S Gohin A Carriero C Chenu AA Pitsillides TR Arnett M Marenzana 《Cell biochemistry and function》2016,34(2):52-62
There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd. 相似文献
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Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c 总被引:3,自引:1,他引:2
Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial
genome, exhibits one of the most heterogeneous rates of amino acid
replacement among placental mammals. Moreover, it has been demonstrated
that cytochrome c oxidase has undergone a structural change in higher
primates which has altered its physical interaction with cytochrome c. We
collected a large data set of COII sequences from several orders of mammals
with emphasis on primates, rodents, and artiodactyls. Using phylogenetic
hypotheses based on data independent of the COII gene, we demonstrated that
an increased number of amino acid replacements are concentrated among
higher primates. Incorporating approximate divergence dates derived from
the fossil record, we find that most of the change occurred independently
along the New World monkey lineage and in a rapid burst before apes and Old
World monkeys diverged. There is some evidence that Old World monkeys have
undergone a faster rate of nonsynonymous substitution than have apes. Rates
of substitution at four-fold degenerate sites in primates are relatively
homogeneous, indicating that the rate heterogeneity is restricted to
nondegenerate sites. Excluding the rate acceleration mentioned above,
primates, rodents, and artiodactyls have remarkably similar nonsynonymous
replacement rates. A different pattern is observed for transversions at
four-fold degenerate sites, for which rodents exhibit a higher rate of
replacement than do primates and artiodactyls. Finally, we hypothesize
specific amino acid replacements which may account for much of the
structural difference in cytochrome c oxidase between higher primates and
other mammals.
相似文献