Metals in Medicine / Biology

A/P Matthew Wilce

UWA

Structural Biology

Computational Biology

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/Chemistry• …

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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 • Electron transport

• photosynthesis

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Cu

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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.

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

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 ??