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Using Solid-State NMR To Monitor the Molecular Consequences of Cryptococcus neoformans Melanization with Different Catecholamine Precursors
journal contribution
posted on 2012-08-07, 00:00 authored by Subhasish Chatterjee, Rafael Prados-Rosales, Susana Frases, Boris Itin, Arturo Casadevall, Ruth E. StarkMelanins are a class of natural pigments associated with
a wide
range of biological functions, including microbial virulence, energy
transduction, and protection against solar radiation. Because of their
insolubility and structural heterogeneity, solid-state nuclear magnetic
resonance (NMR) spectroscopy provides an unprecedented means to define
the molecular architecture of these enigmatic pigments. The requirement
of obligatory catecholamines for melanization of the pathogenic fungus Cryptococcus neoformans also offers unique opportunities
for investigating melanin development. In the current study, pigments
produced with l-dopa, methyl-l-dopa, epinephrine,
and norepinephrine precursors are compared structurally using 13C and 1H magic-angle spinning (MAS) NMR. Striking
structural differences were observed for both aromatic and aliphatic
molecular constituents of the mature fungal pigment assemblies, thus
making it possible to redefine the molecular prerequisites for formation
of the aromatic domains of insoluble indole-based biopolymers, to
rationalize their distinctive physical characteristics, and to delineate
the role of cellular constituents in assembly of the melanized macromolecules
with polysaccharides and fatty acyl chain-containing moieties. By
achieving an augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly,
such studies can guide future drug discovery efforts related to melanin-associated
virulence, resistance to tumor therapy, and production of melanin
mimetics under cell-free conditions.
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13 CCryptococcus neoformans MelanizationMASenergy transductionfungus Cryptococcus neoformansfuture drug discovery effortsassemblymelanized macromoleculesneoformans melanin biosynthesisnorepinephrine precursorspigment assembliestumor therapyvirulenceconstituentNMRDifferent Catecholamine PrecursorsMelaninsmelanin developmentMolecular Consequencesmelanin mimetics
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