title: Relationship between local structure and stability in hen egg white lysozyme mutant with alanine substituted for glycine.
abstract: We prepared five mutant lysozymes in which glycines whose dihedral angles are located in the region of the left-handed helix, Gly49, Gly67, Gly71, Gly102 and Gly117, were mutated to an alanine residue. From analyses of their thermal stabilities using differential scanning calorimetry, most of them were more destabilized than the native lysozyme, except for the G102A mutant, which has a stability similar to that of the native lysozyme at pH 2.7. As for the destabilized mutant lysozymes, their X-ray crystallographic analyses showed that their global structures did not change but that the local structures changed slightly. By examining the dihedral angles at the mutation sites based on X-ray crystallographic results, it was found that the dihedral angles at these mutation sites tended to adopt favorable values in a Ramachandran plot and that the extent and direction of their shifts from the original value had similar tendencies. Therefore, the change in dihedral angles may be the cause of the slight local structural changes around the mutation site. On the other hand, regarding the mutation of G102A, the global structure was almost identical with that of the native structure but the local structure was drastically changed. Therefore, it was suggested that the drastic local conformational change might be effective in releasing the unfavorable interaction of the native state at the mutation site.
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 62 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: K
authors: K
authors: Masumoto
authors: T
authors: T
authors: Ueda
authors: H
authors: H
authors: Motoshima
authors: T
authors: T
authors: Imoto
mesh_terms: D000409:Alanine / Q000737:chemistry; D019943:Amino Acid Substitution; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002645:Chickens; D018360:Crystallography, X-Ray; D004529:Egg White; D005260:Female; D005998:Glycine / Q000737:chemistry; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D009113:Muramidase; D000409:Alanine; D005998:Glycine