Metals in Biology

image011Description: Recent studies have shown that cells use proteins called “metallochaperones” to perform the routing of metal ions to protect the cell and to ensure delivery to nascent enzymes. However, the mechanism of binding and relese of metals by these metallochaperones is not well understood. The largest protein of the copper chaperone family has a common structure known as an “open-faced b-sandwich”, consisting of two a-helices overlaying four b-strands. An exposed –cys-x-x-cys- metal binding motif is positioned in a loop near one end of the protein. A similar motif is seen in the Thioredoxin family of proteins.The cysteinyl thiolates in the Thioredoxin family, with markedly altered pKa’s, serve a catalytic function.

Goals: We are proposing that, as in the Thioredoxin, the thiolates have perturbed pKa’s and these differences are important in the release of the metal ions. A new procedure has been developed to calculate the pKa value of the cysteines in both Thioredoxin and metallochaperones proteins. We use state-of-the art computational chemistry to make such calculations.

Publications

  • Esposito, E. X. et al. Docking Substrates To Metalloenzymes. Molecular Simulation. 24(4-6), 293-306. 2001
  • R. R. Radwan et al. Determination of Cysteine pKas in a Copper Chaperone Protein. Manuscript in preparation, 2004.
  • R. R. Radwan et al., pKa of metalloproteins ligand, Manuscript in preparation, 2004.
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