smith - Applications of Expressed Protein Ligation on the...

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Applications of Expressed Protein Ligation on the KcsA K + Channel Kara Smith October 19, 2005
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Outline Introduction “Semisynthesis of a Functional K + Channel” “Glycine as a D-amino acid surrogate in the K + selectivity filter” Discussion
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Expressed Protein Ligation Schwartz et al, 2003. Chem. Commun. 2087-2090
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KcsA K+ Channel Protein KcsA: K + channel protein from Streptomyces lividans MacKinnon awarded 2003 Nobel Prize for developing 3D structure Very similar to K + channel structure in humans Doyle et al, 1998. Science 280 : 69-77
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Selectivity Filter in K+ Channel Specific to K+ ions only Solvation shell lost as ion enters, stabilized by C=O groups on amino acids More ions, water cavity helps filter K+ through
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Outline Introduction “Semisynthesis of a Functional K + Channel” “Glycine as a D-amino acid surrogate in the K + selectivity filter” Discussion
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First Article: Goals Want to chemically alter K + selectivity filter to understand functional detail Function is related to protein main chain (C=O), must use synthetic chemistry on filter region Problems with current semi-synthetic KcsA channel - Residues 1-125 out of 160 (SPPS limit)
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smith - Applications of Expressed Protein Ligation on the...

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