Transcript Metals in Medicine - University of Sydney

Metals in Medicine / Biology
A/P Matthew Wilce
UWA
Structural Biology
Computational Biology
Molecular Tools
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Crystallography.
NMR.
Mass Spec. Sequencing, proteomics…
Circular Dichroism.
Surface Plasmon Resonance.
Synthesis of drug delivery systems.
Molecular Simulations (using highly parallel software).
in silico drug screening.
Molecular Biology/Protein
Chemistry/Biochemistry/Chemistry
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Plastocyanin
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Plastocyanin
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'blue' copper protein plastocyanin
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from the cyanobacterium Phormidium laminosum
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refined using 2.8 Å X-ray data.
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Plants use light energy to drive electron and proton
transport across the thylakoid membrane.
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Leads to the synthesis of NADPH and ATP utilizing
photosystem I (PSI)1 and II
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(PSII), cytochrome b6/f, and the plastid ATPase,
Plastocyanin
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transfers electrons from cytochrome b6/f to PSI (1)
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Cu
Auracyanin - Chloroflexus aurantiacus
• Electron transport
• photosynthesis
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Ultra Hi-Resolution
Macromolecular Crystallography
• Haloalkane dehalogenase
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1,3,4,6-tetrachloro-1,4-cyclohexadiene hydrolase
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Pseudomonas paucimobilis (Sphingomonas paucimobilis)
• Molecular weight 35kDa, 302 amino acids.
• 0.95Å resolution x-ray diffraction data
• Using synchrotron radiation at the
Advanced Photon Source, IL.
Ultra Hi-Resolution
Haloalkane dehalogenase
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Ultra Hi-Resolution
Haloalkane dehalogenase
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in silico estimation of G of interaction RNA-protein complexes
Poly cytosine RNA
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protein
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Mechanosensitive
Channel - MscL
• Protects bacteria from
osmotic downshock
• A transmembrane channel
that opens to relieve osmotic
pressure
• Gd is known to close the
channel
Engineering ion transport
channels
•Could we in the future use modern molecular biological tools
transiently transfect targetted cells (eg cancer or other disease) to
produce selected ion channels that increase the uptake of
cytotoxic metals ?? Mercury ??