Expression, purification and molecular dynamics simulation of extracellular domain of glucagon-like peptide-2 receptor linked to teduglutide
Expression, purification and molecular dynamics simulation of extracellular domain of glucagon-like peptide-2 receptor linked to teduglutide
نویسندگان: امید جمشیدی کندجانی , علی اکبر علیزاده , سیاوش دستمالچی , سحر صدرخردمند
کلمات کلیدی: Recombinant protein
Glucagon like peptide 2
Teduglutide
Protein characterization
Molecular dynamics simulation
نشریه: 15044 , 1 , 184 , 2021
| نویسنده ثبت کننده مقاله |
سیاوش دستمالچی |
| مرحله جاری مقاله |
تایید نهایی |
| دانشکده/مرکز مربوطه |
مرکز تحقیقات بیوتکنولوژی(زیست فناوری) |
| کد مقاله |
76239 |
| عنوان فارسی مقاله |
Expression, purification and molecular dynamics simulation of extracellular domain of glucagon-like peptide-2 receptor linked to teduglutide |
| عنوان لاتین مقاله |
Expression, purification and molecular dynamics simulation of extracellular domain of glucagon-like peptide-2 receptor linked to teduglutide |
| ناشر |
5 |
| آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ |
بلی |
| عنوان نشریه (خارج از لیست فوق) |
|
| نوع مقاله |
Original Article |
| نحوه ایندکس شدن مقاله |
ایندکس شده سطح یک – ISI - Web of Science |
| آدرس لینک مقاله/ همایش در شبکه اینترنت |
|
| Teduglutide is the only drug approved for long-term treatment of short bowel syndrome (SBS). This drug exerts
its pharmacological effects via binding to the GLP-2 receptors (ECD-GLP2R) located in intestinal tissue. The three
dimensional (3D) structure of ECD-GLP2R hasn't been determined yet and hence its mode of interaction with
agonists/antagonists is not clear. Therefore, it would be of great importance to develop a structural scaffold for
investigation of ECD-GLP2R interactions with its binders. For this, the current study aimed to produce fusion
protein of ECD-GLP2R-teduglutide. The ECD-GLP2R-teduglutide protein was expressed in bacterial expression
system and purified using affinity and size exclusion chromatography techniques. Using circular dichroism the
secondary structure content of purified protein was determined which was comparable to that of theoretical
calculations. The low structural stability of purified protein (ΔG = 3.64 kJ.mol− 1) was elucidated by monitoring
its fluorescence emission at the presence of various concentrations of GdnHCl as a denaturant. Finally, a 3D
model for ECD-GLP2R-teduglutide protein was generated and validated using molecular dynamics simulation
whose information alongside the experimental studies can be useful for providing new insight into the mode of
interaction of ECD-GLP2R with its specific ligands in order to design potent and specific GLP2R agonists. |
| نام فایل |
تاریخ درج فایل |
اندازه فایل |
دانلود |
| Expression, purification and molecular dynamics simulation of extracellular.pdf | 1400/05/09 | 4533608 | دانلود |