理研マンスリーフォーラム

1. "How mother nature fine tunes protein stability?"

Most proteins are globular proteins in which the chain of amino acids folds to give a roughly spherical shape. Consequently, as globular proteins become larger, they bury a larger fraction of their side chains and peptide groups. Based on what we have learned about the stabilizing forces, proteins should become more stable as the size increases. This is not observed: small and large proteins have about the same stability. This suggests that evolution has strategies to keep large proteins from becoming too stable. In an attempt to learn what this strategy is, we compare a small globular protein with just 36 amino acids to a large globular protein with 341 amino acids. Our goal is to gain a better understanding of the means used to keep large proteins from becoming too stable. Our analysis suggests that burying charged groups in the interior of globular proteins is the primary strategy used to fine tune protein stability. Preliminary results from experimental studies designed to test this idea will be discussed.

2. " Factors determining the pK values of the ionizable groups in proteins"

The content and pK values of the ionizable groups of proteins determine the net charge on the protein and make contributions to such important properties as solubility, stability and activity. We have just completed an experimental study of the most important factors that determine the pK values of the ionizable groups of proteins. We will discuss these studies. The pKs depend on the local environment. Groups on the surface of the protein, exposed to solvent, typically have pKs that are close to the intrinsic values observed in model peptides with small perturbations due mainly to electrostatic interactions with other charged groups on the protein. In contrast, the pKs of buried ionizable groups may be substantially perturbed, upward or downward, from model compound values. In addition to electrostatic interactions with other charged groups, these buried groups may be perturbed by the unfavorable Born self energy incurred when a charged group is removed from water and buried in the protein interior in an environment with a lower dielectric constant and by hydrogen bonding. We will show that the pK of a buried carboxyl group can be raised as high as 9 by the Born self energy or lowered to 0.5 by hydrogen bonding.

日時	2007年3月12日（月）15:00〜16:30 （終了しております。）
場所	構造棟セミナーA・B室
演者	Professor C. Nick Pace (Biochemistry and Biophysics, Texas A&M Health Science Center,College Station, TX 77843-1114, USA)
演題	1. "How mother nature fine tunes protein stability?" 2. " Factors determining the pK values of the ionizable groups in proteins" (The talk will be given in English)