Catálogo de publicaciones - revistas

<jats:title>Closing the Loop</jats:title> <jats:p> Many studies have shown that protein dynamics are important to enzyme function. For example, enzyme protein movements have been shown to optimize the active site, enable binding of substrate and cofactor, and facilitate product release. <jats:bold> Whittier <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6148" page="899" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1241735">899</jats:related-article> ) now show that in two tyrosine phosphatases, the rate of cleavage is coupled to motion of a loop. The two phosphatases have different catalytic rates; however, in both, a loop containing a catalytic residue switches between an inactive open and a catalytically competent closed state. The rates of closure are equivalent to the cleavage rates, suggesting that the leaving group tyrosine is protonated simultaneously with loop closure. Thus, tuning of the loop motion plays a regulatory role in the catalytic cycle. </jats:p>

<jats:title>HIV Detection Is a (c)GAS</jats:title> <jats:p> Despite it being one of the most highly studied viruses, there are still many unknowns when it comes to HIV—including how it triggers the innate immune response. <jats:bold> Gao <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6148" page="903" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1240933">903</jats:related-article> , published 8 August) now demonstrate that the DNA sensor cyclic GMP-AMP synthase (cGAS) detects HIV infection. Reverse-transcribed HIV DNA triggers cGAS and downstream activation of antiviral immunity. Detection of HIV, as well as the retroviruses simian immunodeficiency virus and murine leukemia virus, was abrogated in mouse and human cells deficient in cGAS—suggesting that cGAS may be a critical activator of innate immunity in response to retroviral infection. </jats:p>

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<jats:title>Lamins and Tissue Stiffness</jats:title> <jats:p> Microenvironment can influence cell fate and behavior; for example, extracellular matrix (ECM) stiffness increases cell proliferation, and ECM rigidity induces disorders in tissue morphogenesis by increasing cell tension. <jats:bold> Swift <jats:italic>et al.</jats:italic> </jats:bold> ( <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/341/6149/1240104.full">1240104</jats:ext-link> ; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6149" page="965" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1243643"> <jats:bold>Bainer and Weaver</jats:bold> </jats:related-article> ) used proteomics to identify molecules that are mechanical sensors for tissue elasticity in the nucleus and discovered that expression of lamin-A levels apparently functions as a “mechanostat.” </jats:p>

<jats:sec> <jats:title>Background</jats:title> <jats:p> Metal-organic frameworks (MOFs) are made by linking inorganic and organic units by strong bonds (reticular synthesis). The flexibility with which the constituents’ geometry, size, and functionality can be varied has led to more than 20,000 different MOFs being reported and studied within the past decade. The organic units are ditopic or polytopic organic carboxylates (and other similar negatively charged molecules), which, when linked to metal-containing units, yield architecturally robust crystalline MOF structures with a typical porosity of greater than 50% of the MOF crystal volume. The surface area values of such MOFs typically range from 1000 to 10,000 m <jats:sup>2</jats:sup> /g, thus exceeding those of traditional porous materials such as zeolites and carbons. To date, MOFs with permanent porosity are more extensive in their variety and multiplicity than any other class of porous materials. These aspects have made MOFs ideal candidates for storage of fuels (hydrogen and methane), capture of carbon dioxide, and catalysis applications, to mention a few. </jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p> The ability to vary the size and nature of MOF structures without changing their underlying topology gave rise to the isoreticular principle and its application in making MOFs with the largest pore aperture (98 Å) and lowest density (0.13 g/cm <jats:sup>3</jats:sup> ). This has allowed for the selective inclusion of large molecules (e.g., vitamin B <jats:sub>12</jats:sub> ) and proteins (e.g., green fluorescent protein) and the exploitation of the pores as reaction vessels. Along these lines, the thermal and chemical stability of many MOFs has made them amenable to postsynthetic covalent organic and metal-complex functionalization. These capabilities enable substantial enhancement of gas storage in MOFs and have led to their extensive study in the catalysis of organic reactions, activation of small molecules (hydrogen, methane, and water), gas separation, biomedical imaging, and proton, electron, and ion conduction. At present, methods are being developed for making nanocrystals and supercrystals of MOFs for their incorporation into devices. </jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p>The precise control over the assembly of MOFs is expected to propel this field further into new realms of synthetic chemistry in which far more sophisticated materials may be accessed. For example, materials can be envisaged as having (i) compartments linked together to operate separately, yet function synergistically; (ii) dexterity to carry out parallel operations; (iii) ability to count, sort, and code information; and (iv) capability of dynamics with high fidelity. Efforts in this direction are already being undertaken through the introduction of a large number of different functional groups within the pores of MOFs. This yields multivariate frameworks in which the varying arrangement of functionalities gives rise to materials that offer a synergistic combination of properties. Future work will involve the assembly of chemical structures from many different types of building unit, such that the structures’ function is dictated by the heterogeneity of the specific arrangement of their constituents.</jats:p> </jats:sec>