کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8321890 | 1539839 | 2018 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular and in silico analyses validates pathogenicity of homozygous mutations in the NPR2 gene underlying variable phenotypes of Acromesomelic dysplasia, type Maroteaux
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کلمات کلیدی
VMDPDBECDCNPguanylate cyclasediscrete optimized protein energy - انرژی پروتئینی بهینه شده به صورت جداگانهProtein Databank - بانک اطلاعاتی پروتئینProbability density function - تابع چگالی احتمالextracellular domain - دامنه خارج سلولیDiscovery Studio - دیسکاوری استودیوMolecular dynamics - دینامیک ملکولی یا پویایی مولکولیMolecular dynamics simulation - شبیه سازی دینامیک مولکولیHomology model - مدل همولوگاییC-type natriuretic peptide - پپتید سدیم نوعی پتاسیمPdf - پی دی افDOPE - پیش بینی کردن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In the present study, three consanguineous families of Pakistani origin (A, B, C) with variable phenotypes of acromesomelic dysplasia, type Maroteaux were evaluated at clinical and molecular levels. Linkage analysis followed by Sanger sequencing of the NPR2 gene revealed three homozygous mutations including p.(Leu314âArg), p.(Arg371*), and p.(Arg1032*) in family A, B and C, respectively. In silico structural and functional analyses substantiated that a novel missense mutation [p.(Leu314âArg)] in family A allosterically affects binding of NPR2 homodimer to its ligand (CNP) which ultimately results in defective guanylate cyclase activity. A nonsense mutation [p.(Arg371*)] in family B entirely removed the transmembrane domain, protein kinase domain and guanylate cyclase domains of the NPR2 resulting in abolishing its guanylate cyclase activity. Another novel mutation [p.(Arg1032*)], found in family C, deteriorated the guanylate cyclase domain of the protein and probably plundered its guanylate cyclase activity. These results suggest that guanylate cyclase activity is the most critical function of the NPR2 and phenotypic severity of the NPR2 mutations is proportional to the reduction in its guanylate cyclase activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 102, September 2018, Pages 76-86
Journal: The International Journal of Biochemistry & Cell Biology - Volume 102, September 2018, Pages 76-86
نویسندگان
Irfanullah Irfanullah, Amir Zeb, Naila Shinwari, Khadim Shah, Syed Zohaib Tayyab Gilani, Saadullah Khan, Keun Woo Lee, Syed Irfan Raza, Shabir Hussain, Khurram Liaqat, Wasim Ahmad,