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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 • … QuickTime™ and a YUV420 codec decompressor are needed to see this picture. Plastocyanin QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. 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) QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Cu Auracyanin - Chloroflexus aurantiacus • Electron transport • photosynthesis QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. 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 QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Ultra Hi-Resolution Haloalkane dehalogenase QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. in silico estimation of G of interaction RNA-protein complexes Poly cytosine RNA QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. protein QuickTime™ and a YUV420 codec decompressor are needed to see this picture. 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 ??