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排序方式: 共有494条查询结果,搜索用时 31 毫秒
491.
Henzler-Wildman KA Thai V Lei M Ott M Wolf-Watz M Fenn T Pozharski E Wilson MA Petsko GA Karplus M Hübner CG Kern D 《Nature》2007,450(7171):838-844
The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate-enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes. 相似文献
492.
The common biology of cancer and ageing 总被引:1,自引:0,他引:1
At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic--and some say unethical--events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer. 相似文献
493.
Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response
494.
Today, the time-to-market for plastic products ar e getting shorter, thus the lead-time for making the injection mould is decreasin g. There is potential in timesavings in the mould design stage because the design process that is repeatable for every mould design can be standardized. T he preliminary work of any final plastic injection mould design is to always pro vide an initial design of the mould assembly for product designers (customers) p rior to receiving the final product CAD data. Traditiona... 相似文献