Background: The Streptococcus pneumoniae sialidase NanC produces a nonspecific inhibitor of hydrolytic sialidases.Results: The NanC crystal structure is presented in complex with mechanistically relevant ligands.Conclusion: A constricted and hydrophobic active site produces 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA) via a covalent intermediate and direct proton abstraction by a catalytic aspartic acid.Significance: Insights into an unusual reaction mechanism will aid the design of sialidase inhibitors.
The interaction of the extra-membranous domain of tetrameric inwardly rectifying Kir2.1 ion channels (Kir2.1NC(4)) with the membrane associated guanylate kinase protein PSD-95 has been studied using Transmission Electron Microscopy in negative stain. Three types of complexes were observed in electron micrographs corresponding to a 1:1 complex, a large self-enclosed tetrad complex and extended chains of linked channel domains. Using models derived from small angle X-ray scattering experiments in which high resolution structures from X-ray crystallographic and Nuclear Magnetic Resonance studies are positioned, the envelopes from single particle analysis can be resolved as a Kir2.1NC(4):PSD-95 complex and a tetrad of this unit (Kir2.1NC(4):PSD-95)(4). The tetrad complex shows the close association of the Kir2.1 cytoplasmic domains and the influence of PSD-95 mediated self-assembly on the clustering of these channels.
immune responses. Besides the four hydrophobic transmembrane regions, CD81 hosts two extracellular domains, known as large and small extracellular loops (LEL and SEL, respectively). Human CD81 is held to act as (co)receptor for hepatitis C virus (HCV), thus a key participant in the infection. To widen our knowledge on the roles played by CD81 LEL in binding the HCV E2 glycoprotein, the LEL crystal structure was approached. Three different crystal forms have so far been obtained. We report here on the most recently grown form (R32). Marked conformational fluctuations in the molecular regions held to be involved in binding to the viral protein, suggest rules for recognition and assembly within the tetraspan web.
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