Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in ...Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.展开更多
Designing of new peptide materials for biomedical and protein engineering applications are important. In the present work an attempt has been made to study the effect of D-Leu in collagen like tetra peptide on the str...Designing of new peptide materials for biomedical and protein engineering applications are important. In the present work an attempt has been made to study the effect of D-Leu in collagen like tetra peptide on the structure and stability of peptide against enzymes and results are compared with its chiral counterpart L-form. Effect of replacement of L-Leu in Leu-Gly-Pro-Ala tetra peptide with D-Leu on structure has been studied using circular dichroic spectroscopy (CD). Our findings suggest that, D-Leu substitution leads to conformational changes in Leu-Gly-Pro-Ala secondary structure from β-sheet to turns. L → D-Leu Configurational changes in Leu-Gly-Pro-Ala owes to enhanced thermal stability which has been substantiated through CD and differential scanning calorimetry. Change in chirality of the leucine inhibits collagenolytic activity, which enables to design selective inhibition of proteases with greater specificity.展开更多
文摘Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.
文摘Designing of new peptide materials for biomedical and protein engineering applications are important. In the present work an attempt has been made to study the effect of D-Leu in collagen like tetra peptide on the structure and stability of peptide against enzymes and results are compared with its chiral counterpart L-form. Effect of replacement of L-Leu in Leu-Gly-Pro-Ala tetra peptide with D-Leu on structure has been studied using circular dichroic spectroscopy (CD). Our findings suggest that, D-Leu substitution leads to conformational changes in Leu-Gly-Pro-Ala secondary structure from β-sheet to turns. L → D-Leu Configurational changes in Leu-Gly-Pro-Ala owes to enhanced thermal stability which has been substantiated through CD and differential scanning calorimetry. Change in chirality of the leucine inhibits collagenolytic activity, which enables to design selective inhibition of proteases with greater specificity.
