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  • 1
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    Transcription inactivation through local refolding of the RNA polymerase structure (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-24
    Description: Structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure-based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding. Myxopyronin inhibits bacterial RNA polymerase (RNAP) by an unknown mechanism. Here we report the structure of dMyx--a desmethyl derivative of myxopyronin B--complexed with a Thermus thermophilus RNAP holoenzyme. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble. Notably, binding of dMyx stabilizes refolding of the beta'-subunit switch-2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand. Consistently, footprinting data show that the antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. Myxopyronins are thus, to our knowledge, a first structurally characterized class of antibiotics that target formation of the pre-catalytic transcription initiation complex-the decisive step in gene expression control. Notably, mutations designed in switch-2 mimic the dMyx effects on promoter complexes in the absence of antibiotic. Overall, our results indicate a plausible mechanism of the dMyx action and a stepwise pathway of open complex formation in which core enzyme mediates the final stage of DNA melting near the transcription start site, and that switch-2 might act as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics. The universally conserved switch-2 may have the same role in all multisubunit RNAPs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628454/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628454/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belogurov, Georgiy A -- Vassylyeva, Marina N -- Sevostyanova, Anastasiya -- Appleman, James R -- Xiang, Alan X -- Lira, Ricardo -- Webber, Stephen E -- Klyuyev, Sergiy -- Nudler, Evgeny -- Artsimovitch, Irina -- Vassylyev, Dmitry G -- R01 GM058750/GM/NIGMS NIH HHS/ -- R01 GM074252/GM/NIGMS NIH HHS/ -- R01 GM074252-04/GM/NIGMS NIH HHS/ -- R01 GM074840/GM/NIGMS NIH HHS/ -- R01 GM074840-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jan 15;457(7227):332-5. doi: 10.1038/nature07510. Epub 2008 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18946472" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/chemistry/metabolism/pharmacology ; Apoproteins/chemistry ; Binding Sites ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/*chemistry/genetics/*metabolism ; Holoenzymes/chemistry/metabolism ; Lactones/chemistry/metabolism/pharmacology ; Models, Biological ; Models, Molecular ; Molecular Conformation/drug effects ; Mutant Proteins/chemistry/metabolism ; *Protein Folding ; Protein Structure, Tertiary ; Thermus thermophilus/*enzymology/genetics ; Transcription Initiation Site ; *Transcription, Genetic/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    The complex, dusty narrow-line region of NGC 4388: gas-jet interactions, outflows and extinction revealed by near-IR spectroscopy (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-04
    Description: We present Gemini/GNIRS (Gemini Near-Infrared Spectrograph) spectroscopy of the Seyfert 2 galaxy NGC 4388, with simultaneous coverage from 0.85 to 2.5 μm. Several spatially extended emission lines are detected for the first time, both in the obscured and unobscured portion of the optical narrow-line region (NLR), allowing us to assess the combined effects of the central continuum source, outflowing gas and shocks generated by the radio jet on the central 280 pc gas. The H i and [Fe ii ] lines allow us to map the extinction affecting the NLR. We found that the nuclear region is heavily obscured, with E ( B  –  V ) ~ 1.9 mag. To the NE of the nucleus and up to ~150 pc, the extinction remains large, ~1 mag or larger, consistent with the system of dust lanes seen in optical imaging. We derived position–velocity diagrams for the most prominent lines as well as for the stellar component. Only the molecular gas and the stellar component display a well-organized pattern consistent with disc rotation. Other emission lines are kinematically perturbed or show little evidence of rotation. Extended high-ionization emission of sulphur, silicon and calcium is observed to distances of at least 200 pc both NE and SW of the nucleus. We compared flux ratios between these lines with photoionization models and conclude that radiation from the central source alone cannot explain the observed high-ionization spectrum. Shocks between the radio jet and the ambient gas are very likely an additional source of excitation. We conclude that NGC 4388 is a prime laboratory to study the interplay between all these mechanisms.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
    Electronic Resource
    Electronic Resource
    120 and 80 Kd detergent-insoluble glycoproteins as markers of differentiation and adhesion in B16 melanoma
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 140 (1986), S. 638-643 
    Details
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0006-291X(86)90779-5
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  • 4
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    Geology, mineralogy and possible origin of the copper mineralization in marble near Saldán, Córdoba (Argentina) (2012)
    Czech Geological Society
    Details
    Publication Date: 2012-07-15
    Print ISSN: 1802-6222
    Electronic ISSN: 1803-1943
    Topics: Geosciences
    Published by Czech Geological Society
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  • 5
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    THE INTRAGRANITIC POTRERILLOS NYF PEGMATITES AND THEIR A-TYPE HOST GRANITES OF THE LAS CHACRAS - POTRERILLOS BATHOLITH, SIERRA DE SAN LUIS, ARGENTINA (2013)
    Mineralogical Association of Canada
    Details
    Publication Date: 2013-02-01
    Description: The Potrerillos granitic pegmatites, in the Sierras Pampeanas Orientales of San Luis Province, Argentina, consist of mediumsized bodies with rounded, elliptical, or irregular outcrops varying from 10 to 60 m; vertically, they mostly look like thick lenses. Zoning is ill-defined, with a border zone that grades into a coarse-grained intermediate zone. The core zone also is poorly defined, normally containing milky to pink or gray quartz with large crystals of K-feldspar and, locally, pods of primary fluorite. The pegmatite-forming minerals are quartz, microcline and albite, with accessory biotite, muscovite, tourmaline, beryl, allanite, fluorite, fluorapatite, ilmenite, niobian rutile, rutile and pyrite. Rare primary species are monazite-(Ce), U-rich pyrochlore, scheelite, bismuthinite and molybdenite. Subordinate species are hematite, goethite, Mn oxides, clinobisvanite, bismuthite, and opal. The pegmatites are ascribed to the allanite–monazite type, REL–REE subclass, NYF family. Data on melt+fluid inclusion are consistent with crystallization of an aqueous, CO 2 -bearing melt at 475° 〈 T 〈 600°C and ~3.0 to 3.7 kbar, that cooled down to a fluid of low to moderate salinity. The pegmatites are hosted in three dominant facies of two plutons of the Las Chacras – Potrerillos batholith, described as biotite porphyritic granite, biotite-bearing equigranular red granite, and muscovite-bearing equigranular red granite. All of them have high-K compositions, and are metaluminous to mildly peraluminous (ASI in the range 1 to 1.07); the least evolved porphyritic biotite granites of the Las Chacras pluton are depleted in SiO 2 and enriched in TiO 2 , Fe 2 O 3 (T), CaO and MgO, poor in Nb, Rb, Th, and HREE, and enriched in P, Zr, Sr and Ba and LREE relative to the red equigranular muscovite bearing facies of the Potrerillos pluton. The asymmetric REE patterns likely reflect the control by accessory monazite-(Ce) and allanite-(Ce) in the porphyritic facies, contrasting with relative HREE enrichment in the muscovite-bearing equigranular granite. Both granite types display Eu/Eu* values 〈1, indicative of feldspar fractionation in the source; the HREE are strongly depleted, more accentuated in less evolved biotite porphyritic facies, likely reflecting garnet retained in the source. The crystallization-emplacement history of the suite spanned from the Upper Devonian to the Lower Carboniferous in a within-plate regime crossed by deep shear zones. The granite facies that host the pegmatites are redefined as A-type granites. The A-type magmas probably originated by partial melting of a depleted garnet-bearing lower crust, of likely granodiorite or tonalite composition in the minimum melt field of Opx + Cpx + Grt ± Qtz, triggered by mantle-derived heat but previously fertilized by alkali metasomatism produced by mantle degassing.
    Print ISSN: 0008-4476
    Topics: Geosciences
    Published by Mineralogical Association of Canada
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  • 6
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    Mineralogy and Origin of the Dumortierite-Bearing Pegmatites of Virorco, San Luis, Argentina (2012)
    Mineralogical Association of Canada
    Details
    Publication Date: 2012-10-29
    Description: The Virorco dumortierite-bearing pegmatite dikes, in Sierra de San Luis, Eastern Pampean Ranges of central Argentina, are a group of thin, steeply dipping dikes one to 10 cm thick with variable lengths (a few dm to 〈2 m). The pegmatites are emplaced in partially uralitized norite and gabbro that belong to a larger mafic-ultramafic intrusive belt. The pegmatite dikes are symmetrically zoned, with quartz, albite, oligoclase, tourmaline-supergroup and dumortierite-group minerals, muscovite and kyanite as the major phases; the accessory and trace minerals include beryl, chrysoberyl, garnet, fluorapatite, columbite-(Mn) to tantalite-(Mn), pollucite, gahnite, zircon, uraninite and thorite. Holmquistite was found in the exocontact assemblage. Primary textures of magmatic origin were partially disrupted by partial replacements by later minerals and incipient to strong deformation. The whole-rock chemical composition of the dikes shows SiO 2 contents normal for rare-element pegmatites, whereas amounts of Al 2 O 3 and B 2 O 3 are very high. The composition features high MgO, FeO, CaO and P 2 O 5 and, for pegmatites, unusually low Na 2 O and K 2 O contents. Amounts of trace elements are remarkably high in the case of Cs (4.3–94.1 ppm), Ta (130–500) and Be (137–261). The normalized REE contents are low (0.1 to 30 times chondrite), highlighted by a strong negative Eu anomaly. Five textural and compositional types of tourmaline-supergroup minerals were identified in the different pegmatitic zones, ranging from dravite-rich compositions to rossmanite, passing through schorl and Mn-rich elbaite. At least four generations of the dumortierite–holtite minerals are texturally and compositionally represented in these dikes: the earliest dumortierite replaces muscovite and tourmaline, locally together with a second generation that grades into As-poor holtite. The third generation is represented by overgrowths or individual crystals of As-poor and As-rich holtite; it is commonly overgrown by the last generation of dumortierite enriched in As. The chemical evolution of dumortierite-group minerals is characterized by an increase of Ta, Nb and minor As, followed by an extensive enrichment in As (+ Sb + Bi) along with gradual decrease in Ta + Nb. The various assemblages and particularly the compositional trends of tourmaline, dumortierite–holtite and columbite reflect superimposed processes. The initial stage comprises the magmatic crystallization of a highly evolved and boron-rich peraluminous melt. The second stage was a prograde medium-pressure metamorphism, with a fluid-phase-related episode of crystallization. The most likely source of the initial melt is an extraction of residual melt from an almost completely crystallized rare-element parental pegmatite.
    Print ISSN: 0008-4476
    Topics: Geosciences
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  • 7
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    Achalaite, Fe2+TiNb2O8, A New Member of the Wodginite Group From the La Calandria Granitic Pegmatite, Cordoba, Argentina (2017)
    Mineralogical Association of Canada
    Details
    Publication Date: 2017-05-27
    Description: Achalaite is a new mineral of the wodginite group from the La Calandria granitic pegmatite, Cañada del Puerto, Córdoba province, Argentina (31°25'S, 64°55'W). The mineral occurs as polygranular aggregates up to 1.5 cm across, included in albite ± quartz with exsolutions of Ta-rich rutile and intergrown with microlite-group minerals. Achalaite has a black color and streak, metallic luster, H = 51/2, D calc = 6.285 g/cm 3 , and appears to lack cleavage. In reflected light, it is light grey with a slightly violet tint in air, and light grey with an olive tint in oil. Its bireflectance in both air and oil is weak but noticeable. Pleochroism is not observed. With crossed polarizers anisotropy in air is weak, particularly noticeable along grain boundaries; in oil, it is medium with light to intermediate olive grey tint. Internal reflections have not been observed either in air or oil. Data on minimum and maximum reflectances for the COM wavelengths are [ (nm): R air , R oil (%)]: 470: 16.89, 17.72 and 5.26, 5.76; 546: 16.49, 17.26 and 4.98, 5.32; 589: 16.34, 17.04 and 4.97, 5.26; 650: 16.23, 16.94 and 4.86, 5.19. Achalaite, indexed by analogy with wodginite, is monoclinic, space group C 2/ c , Z = 4. Refined unit-cell dimensions are a 9.422(4) Å, b 11.427(3) Å, c 5.120(1) Å, β 90.12° (4), V 551.2(3) Å 3 . The strongest five lines in the X-ray powder diffraction pattern are as follows ( d [Å], I %, hkl ): 3.630, 40, 220; 2.964, 100, , 221; 2.493, 40, 041; 1.735, 40, ; 1.711, 50, , 441. Eight electron microprobe analyses (WDS) gave the following mean composition: WO 3 2.41, Nb 2 O 5 30.18, Ta 2 O 5 37.56, TiO 2 6.90, ZrO 2 0.88, SnO 2 3.82, Fe 2 O 3 4.35, FeO 7.54, MnO 5.14, CaO 0.02, UO 2 0.38, total 99.18 wt.%. The average empirical formula is: (Fe 2+ 2.211 Mn 1.524 Fe 3+ 0.226 U 0.030 Ca 0.009 ) 4.000 (Ti 1.819 Fe 3+ 0.920 Ta 0.579 Sn 0.533 Zr 0.150 ) 4.000 (Nb 4.781 Ta 3.000 W 0.219 ) 8.000 O 32 , ideally Fe 2+ TiNb 2 O 8 . Achalaite is the first member of the wodginite group with Nb dominant over Ta; it is genetically considered a post-magmatic phase. The name of achalaite (CNMNC – IMA 2013-103) derives from the Achala granite batholith, located in Córdoba, Argentina.
    Print ISSN: 0008-4476
    Topics: Geosciences
    Published by Mineralogical Association of Canada
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  • 8
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    Complex Nb-Ta-Ti-Sn Oxide Mineral Intergrowths In The La Calandria Pegmatite, Canada Del Puerto, Cordoba, Argentina (2017)
    Mineralogical Association of Canada
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    Publication Date: 2017-05-27
    Description: The assemblage of Nb-Ta-Ti-Sn oxide minerals in some zoned Devonian granitic pegmatites at the La Calandria mine, Cañada del Puerto, shows complex intergrowths of achalaite, ferrotitanowodginite, Ta-rich rutile, columbite-(Mn), ixiolite, and fluorcalciomicrolite. The chemical composition of these phases is variable, but in general the minerals show slight predominance of Nb over Ta and a clearly defined predominance of Fe over Mn, with minor participation of Ti, Sn, and W. The minerals in this assemblage are not in equilibrium and represent magmatic and subsolidus phases that are distinguished texturally and chemically. The primary magmatic stage of mineralization possibly crystallized ixiolite + Ta-rich rutile I in the outer zones of the pegmatite and, less commonly, local columbite-(Mn) in the inner part. Subsolidus unmixing of ixiolite produced achalaite and ferrotitanowodginite I + Ta-rich rutile II. Contemporaneously, Ta-rich rutile I locally exsolved ferrotitanowodginite/achalaite II + cassiterite. A localized Ca-F-rich hydrothermal overprinting event transformed Ta-rich rutile I to Ta-rich rutile III + ferrotitanowodginite/achalaite II + fluorcalciomicrolite. Furthermore, the hydrothermal overprint produced peripheral transformation of columbite-(Mn) to possibly achalaite III and widespread distribution of fluorcalciomicrolite throughout the assemblage.
    Print ISSN: 0008-4476
    Topics: Geosciences
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  • 9
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    Mineralogy and crystal chemistry of micas from the A-type El Portezuelo Granite and related pegmatites, Catamarca (NW Argentina) (2012)
    Czech Geological Society
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    Publication Date: 2012-07-15
    Print ISSN: 1802-6222
    Electronic ISSN: 1803-1943
    Topics: Geosciences
    Published by Czech Geological Society
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  • 10
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    Na-Fe-Ca Alteration and LREE (Th-Nb) Mineralization in Marble andGranitoids of Sierra de Sumampa, Santiago del Estero, Argentina (2005)
    Society of Economic Geologists
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    Publication Date: 2005-06-01
    Print ISSN: 0361-0128
    Electronic ISSN: 1554-0774
    Topics: Geosciences
    Published by Society of Economic Geologists
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