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PNAS Plus Significance Statements PNAS PLUS PNAS PLUS PNAS Plus Significance Statements PNAS PLUS Recombinant silicateins as model biocatalysts in properties, occurring on attosecond timescales on up − organosiloxane chemistry (1 as = 10 18 s). The recent development of attosecond S. Yasin Tabatabaei Dakhili, Stephanie A. Caslin, Abayomi S. angle-resolved photoemission spectroscopy (atto- Faponle, Peter Quayle, Sam P. de Visser, and Lu Shin Wong ARPES) using high harmonic generation has opened – Organosiloxanes are components in a huge variety of up the possibility of probing electron electron interact- – consumer products and play a major role in the syn- ions in real time. In this paper, we distinguish electron thesis of fine chemicals. However, their synthetic electron screening and charge scattering in the time manipulation primarily relies on the use of chloro- domain in individual energy bands within a solid. silanes, which are energy-intensive to produce and These results open up new possibilities for probing – environmentally undesirable. Synthetic routes that fundamental electron electron interactions in a host of operate under ambient conditions and circumvent the materials including magnetic, superconducting, and – need for chlorinated feedstocks would therefore offer advanced quantum materials. (See pp. E5300 E5307.) a more sustainable route for producing this class of compounds. Here, a systematic survey is reported for Application of metabolic controls for the the silicatein enzyme, which is able to catalyze the maximization of lipid production in hydrolysis, condensation, and exchange of the sili- semicontinuous fermentation con–oxygen bond in a variety of organosiloxanes Jingyang Xu, Nian Liu, Kangjian Qiao, Sebastian Vogg, under environmentally benign conditions. These re- and Gregory Stephanopoulos sults suggest that silicatein is a promising candidate This work establishes a semicontinuous process for for development of selective and efficient biocatalysts efficient and complete upgrading of low-strength for organosiloxane chemistry. (See pp. E5285–E5291.) acetic acid into lipids. By implementing control strategies in response to the time-varying nature of Transitional–turbulent spots and turbulent– cell metabolism, we achieved and sustained lipid turbulent spots in boundary layers yields close to the theoretical maximum while main- taining high productivities. The control algorithm was Xiaohua Wu, Parviz Moin, James M. Wallace, Jinhie Skarda, Adrián Lozano-Durán, and Jean-Pierre Hickey designed to respond to readily available real-time measurements and basic principles, which is ideal for Uncovering the constitutive coherent structure in the in- industrial applications. Overall, our process scheme ner layer of the canonical turbulent boundary layer has can directly take in dilute nutrient streams that are remained a central fluid mechanics theme, because it difficult and costly to purify and is able to biologically tests our intellectual ability to understand even the sim- convert them into highly concentrated value-added plest external flow. We describe here how turbulent spots products. This design significantly reduces the energy are initiated in bypass boundary-layer transition and un- costs associated with processes using dilute feed- cover the ubiquity of concentrations of vortices in the fully stocks, which typically require initial concentration of turbulent region with characteristics remarkably like tran- the feed. (See pp. E5308–E5316.) sitional–turbulent spots. We present strong evidence that these concentrations of vortices are the constitutive co- Tetrahydrobiopterin regulates monoamine herent structure of the inner layer near the wall. This study neurotransmitter sulfonation contributes to the unification of understanding of phe- nomena occurring in boundary-layer late-stage transition Ian Cook, Ting Wang, and Thomas S. Leyh with near-wall turbulent boundary-layer structure and Human cytosolic sulfotransferases (SULTs) regulate dynamics in the developed flow. (See pp. E5292–E5299.) hundreds of signaling small molecules, yet little is known regarding their small-molecule regulation. Distinguishing attosecond electron–electron Members of the SULT1 family harbor a conserved scattering and screening in transition metals allosteric site that we hypothesize allows independent regulation of sulfonation in the 11 metabolic areas in Cong Chen, Zhensheng Tao, Adra Carr, Piotr Matyba, Tibor Szilvási, Sebastian Emmerich, Martin Piecuch, Mark Keller, Dmitriy which these isoforms operate. This hypothesis is val- Zusin, Steffen Eich, Markus Rollinger, Wenjing You, Stefan idated using SULT1A3, which sulfonates and inactivates Mathias, Uwe Thumm, Manos Mavrikakis, Martin Aeschlimann, monoamine neurotransmitters. During validation it was Peter M. Oppeneer, Henry Kapteyn, and Margaret Murnane discovered that tetrahydrobiopterin (THB), an essential Electron–electron interactions are among the fastest cofactor in monoamine neurotransmitter biosynthesis, processes in materials that determine their fascinating allosterically inhibits SULT1A3 with high affinity (Ki,23nM) www.pnas.org/cgi/doi/10.1073/pnas.ss11427 PNAS | July 3, 2017 | vol. 114 | no. 27 | 6891–6894 Downloaded by guest on September 24, 2021 and isozyme selectivity. Monoamine neurotransmitter metabolism C2B–SNAP25 and Rph3A C2B–PIP2 complexes, we revealed a shapes human behavior and social interactions and is a thera- membrane-binding mode in which the Rph3A-C2 domains operate 2+ peutic target. These findings provide a paradigm for regulating in cooperation with PIP2/Ca and SNAP25, adopting a confor- sulfonation and a target for controlling neurotransmitter activity. mation able to promote membrane bending, suggesting a model (See pp. E5317–E5324.) to explain how Rph3A regulates various steps of the vesicle fusion process. (See pp. E5343–E5351.) Structure of human Fe–S assembly subcomplex reveals unexpected cysteine desulfurase architecture and Uncovering BRD4 hyperphosphorylation associated with acyl-ACP–ISD11 interactions cellular transformation in NUT midline carcinoma Seth A. Cory, Jonathan G. Van Vranken, Edward J. Brignole, Shachin Patra, Ranran Wang, Xing-Jun Cao, Katarzyna Kulej, Wei Liu, Tongcui Ma, Margo Dennis R. Winge, Catherine L. Drennan, Jared Rutter, MacDonald, Cheng-Ming Chiang, Benjamin A. Garcia, and Jianxin You and David P. Barondeau BRD4 plays a vital role in cellular growth control. Because BRD4 is Prokaryotic and eukaryotic organisms use analogous pathways dysregulated in a wide range of aggressive malignancies, it is to synthesize protein cofactors called iron–sulfur clusters. An being increasingly implicated as a major driver of oncogenic unexplained difference between pathways is the functional re- growth and a novel target for cancer therapy. However, how quirements of the respective cysteine desulfurases. In eukary- BRD4 is regulated to maintain its normal function in healthy cells otes, the cysteine desulfurase NFS1 requires additional accessory and how alteration of this process leads to cancer remain poorly subunits for function. The lack of structural information has lim- understood. We discovered that BRD4 is hyperphosphorylated in ited mechanistic insight into the role of these accessory proteins cancers and that this hyperphosphorylation may be a general in mitochondrial Fe–S cluster biosynthesis. Here we determined mechanism to support its oncogenic activities. Our study shows crystallographic and electron microscopic structures of the how dysregulation of BRD4 function could lead to tumorigene- NFS1–ISD11–ACP subcomplex. These results reveal an unex- sis. Our discovery also provides the rationale for investigating pected cysteine desulfurase architecture that reconciles mecha- how cellular signaling pathways modulate BRD4 phosphorylation nistic differences between the prokaryotic and eukaryotic systems, to control its function during cancer development. (See pp. reveals the basis of control of iron–sulfur cluster assembly through E5352–E5361.) fatty acid synthesis, and serves as a structural foundation for in- vestigating human diseases related to iron–sulfur cluster assembly. Bacteria-mediated hypoxia functions as a signal for (See pp. E5325–E5334.) mosquito development Kerri L. Coon, Luca Valzania, David A. McKinney, Kevin J. Vogel, Mark R. Role of the CBP catalytic core in intramolecular Brown, and Michael R. Strand SUMOylation and control of histone H3 acetylation Mosquitoes are important insects because several species transmit Sangho Park, Robyn L. Stanfield, Maria A. Martinez-Yamout, H. Jane pathogens as adults that cause disease in humans and other verte- Dyson, Ian A. Wilson, and Peter E. Wright brates. One approach for control is preventing immature mosquitoes CREB-binding protein (CBP) and its paralog p300 play a vital role from developing into adults. Immature-stage mosquitoes require gut in regulating gene transcription. Through the enzymatic activ- bacteria to develop, but the mechanisms underlying this de- ity of their histone acetyltransferase (HAT) domain, CBP and pendence are unknown. Here, we identify cytochrome bd oxidase as p300 control the accessibility of genes in chromatin and activate a bacterial product involved in mosquito development. We also transcription. They also function as transcriptional repressors show that bacteria-mediated reduction of oxygen levels in the di- following SUMOylation of the cell cycle regulatory domain 1 gestive tract of larvae serves as a signal for molting. These findings (CRD1) located N-terminal
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