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.
- 20 -
