ch04 - 2/7/2011 Protein Structure Chapter 4 3-23 X-Ray...

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2/7/2011 1 Protein Structure Chapter 4 3-23 X-Ray Crystallography “If a picture is worth a thousand words, then a macromolecular structure is priceless to a physical biochemist.” – van Holde Science 5 January 2007: Vol. 315. no. 5808, pp. 40 - 41 Chemistry Nobel Rich in Structure …In particular, there were 12 Nobel Prizes in chemistry and physiology or medicine awarded for work in this field from 1956 to 2006 (table S1) ( 2 ). Almost one in four chemistry prizes since 1956 have been for structure work, and in the last decade, fully half have dealt with work related to macromolecular structure. …From 1970 to 2006, 4% of all chemistry publications dealt with crystallography, yet this subfield captured 19% of the available Nobel Prizes (table S3) ( 2 ). During the past decade, crystallography papers represented 7% of all chemistry publications, but commanded 4 of 10 available prizes.
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2/7/2011 2 Structural Analysis has Revolutionized Biochemistry and the Life Sciences
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2/7/2011 3 The X-ray Method 1. Grow USEFUL crystals from purified protein 2. Collect X-ray diffraction data ; these are only the amplitudes of a complex number 3. The PHASE problem (recover information lost in detection) 4. Build the model, validate it, and interpret the results.
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2/7/2011 4 Object / Real Space Transform / Reciprocal Space Object Transform Image Models Electron Density Maps
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2/7/2011 5 There are several structural projects currently under study in our laboratory • Structure-based “drug” design for ricin • Structure-based inhibitor design for flu • Structure and action of translin and Trax • Anti-fungal design for Methionine Synthase • Inhibitor binding to DDAH RTA has a specificity pocket within a large, polar, active site cleft
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2/7/2011 6 In Feb, 2004 Ricin provided me 30 seconds of fame 3-13 Back to the analysis of higher structure Amino acids condense to form polypeptides primary structure.
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ch04 - 2/7/2011 Protein Structure Chapter 4 3-23 X-Ray...

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