Stability and solvation of Thr/Ser to Ala and Gly mutations at the N-cap of alpha-helices.
The solvation of polar groups at the N-terminal end of alpha-helices was studied by comparing the crystal structures of T4 lysozyme, barley chymotrypsin inhibitor 2 (CI2), barnase and their respective N-cap mutants. Whether or not the N3 residue is solvated on mutating the N-cap Thr/Ser to Ala or Gly appears to be related to the identities and the side-chain conformations of the N2 and N3 residues. When these two residues are alanines, as is in the pseudo-wild-type CI2 (E33A/E34A), the main-chain NH at the N3 position is exposed to the solvent and can be solvated. If the N2 residue is an Asp or a Glu, it is more likely that the side-chain of these residues will form a surrogate N-cap with the amide NH at N3 to compensate for the lost -OH group. In this case, no additional solvation will be observed. In general, Gly can be more stable than Ala at the N-cap because its small side-chain allows nearby polar groups to form hydrogen bonds with optimal geometry with solvent molecules or other polar groups.
Centre for Protein Engineering, Medical Research Council Centre, Cambridge, UK.
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Chen
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Fersht
D001426:Bacterial Proteins; D017122:Bacteriophage T4 / Q000201:enzymology; D003198:Computer Simulation; D003460:Crystallization; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D010455:Peptides; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012260:Ribonucleases / Q000737:chemistry* / Q000235:genetics; D012997:Solvents; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D010455:Peptides; D010940:Plant Proteins; D012997:Solvents; C093336:chymotrypsin inhibitor 2; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D009113:Muramidase