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521.
Fernando Porcelli Doriana Triggiani Bethany A. Buck-Koehntop Larry R. Masterson Gianluigi Veglia 《Journal of biological inorganic chemistry》2009,14(8):1219-1225
We investigated the time dependence of the degradation of three alkyltin derivatives by a nine amino acid linear peptide (I1LGCWCYLR9) containing a CXC motif derived from the primary sequence of stannin, a membrane protein involved in alkyltin toxicity. We
monitored the reaction kinetics using the intrinsic fluorescence of the tryptophan residue in position 5 of the peptide and
found that all of the alkyltins analyzed are progressively degraded to dialkyl derivatives, following a pseudoenzymatic reaction
mechanism. The end point of the reactions is the formation of a covalent complex between the disubstituted alkyltin and the
peptide cysteines. These data agree with the speciation profiles proposed for polysubstituted alkyltins in the environment
and reveal a possible biotic degradation pathway for these toxic compounds. 相似文献
522.
Hope E. Stansfield Bethany P. Kulczewski Kyle E. Lybrand Elizabeth R. Jamieson 《Journal of biological inorganic chemistry》2009,14(2):193-199
Protein microarrays have been used extensively to identify protein–protein interactions; however, this technology has not
been widely applied to protein–DNA interactions. In particular, this work demonstrates the utility of this technique for rapidly
identifying interactions of proteins with metal-modified DNA. Protein macroarray experiments were carried out with high mobility
group protein 1 (HMG-1) and cisplatin- and chromium-modified 50-mer oligonucleotides to demonstrate “proof of principle.”
Commercially available protein microarrays containing many different classes of human proteins were then employed to search
for additional interactions with cisplatin-modified DNA. The results of the microarray experiments confirmed some known interactions
and, more importantly, identified many novel protein interactions, demonstrating the utility of this method as a rapid, high-throughput
technique to discover proteins that interact with metal-modified DNA.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Bethany J. Slater Karen J. Liu Matthew D. Kwan Natalina Quarto Michael T. Longaker 《PloS one》2009,4(1)
Background
The tremendous diversity in vertebrate skull formation illustrates the range of forms and functions generated by varying genetic programs. Understanding the molecular basis for this variety may provide us with insights into mechanisms underlying human craniofacial anomalies. In this study, we provide evidence that the anuran Xenopus laevis can be developed as a simplified model system for the study of cranial ossification and suture patterning. The head structures of Xenopus undergo dramatic remodelling during metamorphosis; as a result, tadpole morphology differs greatly from the adult bony skull. Because of the extended larval period in Xenopus, the molecular basis of these alterations has not been well studied.Methodology/Principal Findings
We examined late larval, metamorphosing, and post-metamorphosis froglet stages in intact and sectioned animals. Using micro-computed tomography (μCT) and tissue staining of the frontoparietal bone and surrounding cartilage, we observed that bone formation initiates from lateral ossification centers, proceeding from posterior-to-anterior. Histological analyses revealed midline abutting and posterior overlapping sutures. To determine the mechanisms underlying the large-scale cranial changes, we examined proliferation, apoptosis, and proteinase activity during remodelling of the skull roof. We found that tissue turnover during metamorphosis could be accounted for by abundant matrix metalloproteinase (MMP) activity, at least in part by MMP-1 and -13.Conclusion
A better understanding of the dramatic transformation from cartilaginous head structures to bony skull during Xenopus metamorphosis may provide insights into tissue remodelling and regeneration in other systems. Our studies provide some new molecular insights into this process. 相似文献525.
In many tumor cells, the activation and activity of extracellular signal-regulated kinases (ERK1/2) are very high because of the constitutive activation of the Ras-mediated signaling pathway. Here, we ectopically expressed the human homologue of rat eukaryotic initiation factor 2-associated glycoprotein, p67/MetAP2, in EGF-treated mouse embryonic NIH3T3 fibroblasts and C2C12 myoblasts and NIH3T3 cell lines expressing the constitutively active form of MAP kinase kinase (MEK) to inhibit the activation and activity of ERK1/2 MAP kinases. In addition, we also ectopically expressed rat p67/MetAP2 in oncogenic Ras-induced transformed NIH3T3 fibroblasts and inhibited their transformed phenotype both in culture and in athymic nude mice possibly by inhibiting angiogenesis. This inhibition of ERK1/2 MAP kinases is due to the direct binding with rat p67/MetAP2, and this leads to the inhibition of activity of ERK1/2 MAP kinases both in vitro and in vivo. Furthermore, expression of p67/MetAP2 siRNA in both NIH3T3 fibroblasts and C2C12 myoblasts causes activation and activity of ERK1/2 MAP kinases. Our results thus suggest that ectopic expression of rat p67/MetAP2 in transformed cells can inhibit the tumorigenic phenotype by inhibiting the activation and activity of ERK1/2 MAP kinases and, thus, that p67/MetAP2 has tumor suppression activity. 相似文献
526.
Paul A. Del Rizzo Jean-Fran?ois Couture Lynnette M. A. Dirk Bethany S. Strunk Marijo S. Roiko Joseph S. Brunzelle Robert L. Houtz Raymond C. Trievel 《The Journal of biological chemistry》2010,285(41):31849-31858
SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine ϵ-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine ϵ-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated ϵ-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes. 相似文献
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