Metals in Medicine / Biology

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Metals in Medicine / Biology

• A/P Matthew Wilce
• UWA
• Structural Biology
• Computational Biology

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Molecular Tools

• 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/C
  hemistry

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Plastocyanin
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Plastocyanin

• 'blue' copper protein plastocyanin
• from the cyanobacterium Phormidium laminosum
• refined using 2.8 Å X-ray data.
• Plants use light energy to drive electron and
  proton transport across the thylakoid membrane.
• Leads to the synthesis of NADPH and ATP utilizing
  photosystem I (PSI)1 and II
• (PSII), cytochrome b6/f, and the plastid ATPase,
  Plastocyanin
• transfers electrons from cytochrome b6/f to PSI
  (1)

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Auracyanin - Chloroflexus aurantiacus
Cu

• Electron transport
• photosynthesis

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Ultra Hi-Resolution Macromolecular Crystallography

• Haloalkane dehalogenase
• 1,3,4,6-tetrachloro-1,4-cyclohexadiene hydrolase
• 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.

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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
XXXXXX...XXXCCCCCCXXX...XXXX
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

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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 ??