Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Thursday Abstracts

Methyl Transfer from AdoMet by a Knotted Protein Fold Ya-Ming Hou . Thomas Jefferson University, Philadelphia, USA.

TrmD is a bacteria-specific tRNA methyl transferase that transfers the methyl group from AdoMet to the N1 of G37-tRNA. The reaction product of TrmD, m1G37-tRNA, is essential for growth and it maintains the reading frame accuracy during tRNA translation on the ribosome. TrmD binds AdoMet using a rare trefoil-knot protein fold, whereas Trm5, the eukaryotic counterpart of TrmD, binds AdoMet using a common Rossmann-fold. While TrmD and Trm5 are fundamentally distinct in the AdoMet domain, we ask the question whether they are distinct in the catalytic mechanism. This is important for understanding the relationship of these two enzymes. Using pre-steady-state kinetic assays, we show that these two enzymes are distinct and unrelated in all aspects of the reaction mechanism. The striking distinction between these two enzymes supports the notion that TrmD is an attractive target for antibacterial discovery.

Harvesting the Fruits of the Energy Landscape Theory of Protein Folding Peter G. Wolynes Rice University, Houston, Texas

Protein folding can be understood as a biased search on a funneled but rugged energy landscape. This picture can be made quantitative using the statistical mechanics of glasses and first order transitions in mesoscopic systems. The funneled nature of the protein energy landscape is a consequence of natural selection. I will discuss how this rather simple picture quantitatively predicts folding mechanism from native structure and sequence. I will also discuss recent advances using energy landscape ideas to create algorithms capable of predicting protein tertiary structure from sequence, protein binding sites and the nature of structurally specific protein misfolding relevant to disease.

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