B9(Ser→Asp) insulin, one of the fast-acting insulin mutants produced by protein engineering, has been crystallized. Three crystal forms have been obtained, which belong to orthorhombic, tetragonal and rhombohedral sy...B9(Ser→Asp) insulin, one of the fast-acting insulin mutants produced by protein engineering, has been crystallized. Three crystal forms have been obtained, which belong to orthorhombic, tetragonal and rhombohedral system, respectively. Each crystal form contains different aggregation units of the mutant, i.e. dimer or hexamer. The diffraction data of the former two have been collected beyond 0.2 nm resolution. The structural analyses and comparisons will provide some information about insulin’s self-association and the structural basis of the fast absorption produced from the mutation.展开更多
It has long been found that insulin in acid solution is unstable. The main reason is that the A-chain C-terminal residue, asparagine, is very susceptible to acid hydrolysis, thereby a covalent-dimer formation takes pl...It has long been found that insulin in acid solution is unstable. The main reason is that the A-chain C-terminal residue, asparagine, is very susceptible to acid hydrolysis, thereby a covalent-dimer formation takes place readily due to the deamidation of this residue. As a number of pharmaceutical preparations of insulin are acidic solutions, this kind of instability has brought about a serious problem on purity and storage of this preparation in展开更多
Ⅰ. INTRODUCTIONThe chemical stability of human insulin preparations is directly related to the residue of A21-Asn at C-terminal of A chain and can be distinctly increased by substituting the A21 residue in the way of...Ⅰ. INTRODUCTIONThe chemical stability of human insulin preparations is directly related to the residue of A21-Asn at C-terminal of A chain and can be distinctly increased by substituting the A21 residue in the way of protein engineering. Studying the fine three-dimensional structures展开更多
Butyrylcholinesterase (BChE) is an enzyme which has been shown to be involved in the patho-genesis, treatment and prognosis of Alzheimer’s disease. In its current form, however, evidence is equivocal with all of the ...Butyrylcholinesterase (BChE) is an enzyme which has been shown to be involved in the patho-genesis, treatment and prognosis of Alzheimer’s disease. In its current form, however, evidence is equivocal with all of the associations. Variant forms of the protein exist, where the enzymatic function is lost to varying degrees. We performed in silico evaluation of these variants. Bioinformatics and molecular modeling, based on data from ESTHER database and Protein Data Bank (RCSB), were used for in silico predictions of the structures of the silent variants that involve a single amino acid change. Variants with loss of enzyme activity were evaluated for structural changes near the active site and the thermody-namic stability of the variants was estimated. The results indicated that the loss of activity of the variants can, in most cases, be attributed to structural changes in the active site or to lower thermodynamic stability. Our results showed that the loss of enzyme activity may be due to changes in the active site, oligomerization or loss of structural stability. Individuals with loss of function mutation of BChE can be studied and followed up for their proneness or resistance to cognitive decline with aging.展开更多
文摘B9(Ser→Asp) insulin, one of the fast-acting insulin mutants produced by protein engineering, has been crystallized. Three crystal forms have been obtained, which belong to orthorhombic, tetragonal and rhombohedral system, respectively. Each crystal form contains different aggregation units of the mutant, i.e. dimer or hexamer. The diffraction data of the former two have been collected beyond 0.2 nm resolution. The structural analyses and comparisons will provide some information about insulin’s self-association and the structural basis of the fast absorption produced from the mutation.
基金Project supported by UNIDO(91/048)and High-Tech Program of China(103-19-01).
文摘It has long been found that insulin in acid solution is unstable. The main reason is that the A-chain C-terminal residue, asparagine, is very susceptible to acid hydrolysis, thereby a covalent-dimer formation takes place readily due to the deamidation of this residue. As a number of pharmaceutical preparations of insulin are acidic solutions, this kind of instability has brought about a serious problem on purity and storage of this preparation in
基金Project supported by the UNIDO(91/048/)and the "863" High-Tech Plan of China.
文摘Ⅰ. INTRODUCTIONThe chemical stability of human insulin preparations is directly related to the residue of A21-Asn at C-terminal of A chain and can be distinctly increased by substituting the A21 residue in the way of protein engineering. Studying the fine three-dimensional structures
文摘Butyrylcholinesterase (BChE) is an enzyme which has been shown to be involved in the patho-genesis, treatment and prognosis of Alzheimer’s disease. In its current form, however, evidence is equivocal with all of the associations. Variant forms of the protein exist, where the enzymatic function is lost to varying degrees. We performed in silico evaluation of these variants. Bioinformatics and molecular modeling, based on data from ESTHER database and Protein Data Bank (RCSB), were used for in silico predictions of the structures of the silent variants that involve a single amino acid change. Variants with loss of enzyme activity were evaluated for structural changes near the active site and the thermody-namic stability of the variants was estimated. The results indicated that the loss of activity of the variants can, in most cases, be attributed to structural changes in the active site or to lower thermodynamic stability. Our results showed that the loss of enzyme activity may be due to changes in the active site, oligomerization or loss of structural stability. Individuals with loss of function mutation of BChE can be studied and followed up for their proneness or resistance to cognitive decline with aging.
