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  • 1
    Online Resource
    Online Resource
    Observation of the controlled assembly of preclick components in the in situ click chemistry generation of a chitinase inhibitor
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 40 ( 2013-10), p. 15892-15897
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 40 ( 2013-10), p. 15892-15897
    Abstract: The Huisgen cycloaddition of azides and alkynes, accelerated by target biomolecules, termed “in situ click chemistry,” has been successfully exploited to discover highly potent enzyme inhibitors. We have previously reported a specific Serratia marcescens chitinase B ( Sm ChiB)-templated syn -triazole inhibitor generated in situ from an azide-bearing inhibitor and an alkyne fragment. Several in situ click chemistry studies have been reported. Although some mechanistic evidence has been obtained, such as X-ray analysis of [protein]–[“click ligand”] complexes, indicating that proteins act as both mold and template between unique pairs of azide and alkyne fragments, to date, observations have been based solely on “postclick” structural information. Here, we describe crystal structures of Sm ChiB complexed with an azide ligand and an O -allyl oxime fragment as a mimic of a click partner, revealing a mechanism for accelerating syn -triazole formation, which allows generation of its own distinct inhibitor. We have also performed density functional theory calculations based on the X-ray structure to explore the acceleration of the Huisgen cycloaddition by Sm ChiB. The density functional theory calculations reasonably support that Sm ChiB plays a role by the cage effect during the pretranslation and posttranslation states of selective syn -triazole click formation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1315049110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell–derived neocortex
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 50 ( 2013-12-10), p. 20284-20289
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 50 ( 2013-12-10), p. 20284-20289
    Abstract: Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaudal-ventrorostral axis and undergoes region-specific rolling morphogenesis that generates a semispherical structure. The neuroepithelium self-forms a multilayered structure including three neuronal zones (subplate, cortical plate, and Cajal-Retzius cell zones) and three progenitor zones (ventricular, subventricular, and intermediate zones) in the same apical-basal order as seen in the human fetal cortex in the early second trimester. In the cortical plate, late-born neurons tend to localize more basally to early-born neurons, consistent with the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone contains basal progenitors that share characteristics with outer radial glia abundantly found in the human, but not mouse, fetal brain. Thus, human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1315710110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    ADP-ribosylation factor machinery mediates endocytosis in plant cells
    Proceedings of the National Academy of Sciences ; 2010
    In:  Proceedings of the National Academy of Sciences Vol. 107, No. 50 ( 2010-12-14), p. 21890-21895
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 50 ( 2010-12-14), p. 21890-21895
    Abstract: Endocytosis is crucial for various cellular functions and development of multicellular organisms. In mammals and yeast, ADP-ribosylation factor (ARF) GTPases, key components of vesicle formation, and their regulators ARF-guanine nucleotide exchange factors (GEFs) and ARF-GTPase-activating protein (GAPs) mediate endocytosis. A similar role has not been established in plants, mainly because of the lack of the canonical ARF and ARF-GEF components that are involved in endocytosis in other eukaryotes. In this study, we revealed a regulatory mechanism of endocytosis in plants based on ARF GTPase activity. We identified that ARF-GEF GNOM and ARF-GAP VASCULAR NETWORK DEFECTIVE 3 (VAN3), both of which are involved in polar auxin transport-dependent morphogenesis, localize at the plasma membranes as well as in intracellular structures. Variable angle epifluorescence microscopy revealed that GNOM and VAN3 localize to partially overlapping discrete foci at the plasma membranes that are regularly associated with the endocytic vesicle coat clathrin. Genetic studies revealed that GNOM and VAN3 activities are required for endocytosis and internalization of plasma membrane proteins, including PIN-FORMED auxin transporters. These findings identified ARF GTPase-based regulatory mechanisms for endocytosis in plants. GNOM and VAN3 previously were proposed to function solely at the recycling endosomes and trans -Golgi networks, respectively. Therefore our findings uncovered an additional cellular function of these prominent developmental regulators.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1016260107
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2010
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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