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المؤلفAgrahari, Ashish Kumar
المؤلفKrishna Priya, M
المؤلفPraveen Kumar, Medapalli
المؤلفTayubi, Iftikhar Aslam
المؤلفSiva, R
المؤلفPrabhu Christopher, B
المؤلفGeorge Priya Doss, C
المؤلفZayed, Hatem
تاريخ الإتاحة2019-03-06T05:17:22Z
تاريخ النشر2019-02-01
اسم المنشورComputers in Biology and Medicine
المعرّفhttp://dx.doi.org/10.1016/j.compbiomed.2019.02.014
الاقتباسAgrahari AK, Krishna Priya M, Praveen Kumar M, Tayubi IA, Siva R, Prabhu Christopher B, George Priya Doss C, Zayed H. Understanding the structure-function relationship of HPRT1 missense mutations in association with Lesch-Nyhan disease and HPRT1-related gout by in silico mutational analysis. Comput Biol Med. 2019 Feb 23;107:161-171. doi: 10.1016/j.compbiomed.2019.02.014.
الرقم المعياري الدولي للكتاب0010-4825
معرّف المصادر الموحدhttp://hdl.handle.net/10576/11375
الملخصThe nucleotide salvage pathway is used to recycle degraded nucleotides (purines and pyrimidines); one of the enzymes that helps to recycle purines is hypoxanthine guanine phosphoribosyl transferase 1 (HGPRT1). Therefore, defects in this enzyme lead to the accumulation of DNA and nucleotide lesions and hence replication errors and genetic disorders. Missense mutations in hypoxanthine phosphoribosyl transferase 1 (HPRT1) are associated with deficiencies such as Lesch-Nyhan disease and chronic gout, which have manifestations such as arthritis, neurodegeneration, and cognitive disorders. In the present study, we collected 88 non-synonymous single nucleotide polymorphisms (nsSNPs) from the UniProt, dbSNP, ExAC, and ClinVar databases. We used a series of sequence-based and structure-based in silico tools to prioritize and characterize the most pathogenic and stabilizing or destabilizing nsSNPs. Moreover, to obtain the structural impact of the pathogenic mutations, we mapped the mutations to the crystal structure of the HPRT protein. We further subjected these mutant proteins to a 50 ns molecular dynamics simulation (MDS). The MDS trajectory showed that all mutant proteins altered the structural conformation and dynamic behavior of the HPRT protein and corroborated its association with LND and gout. This study provides essential information regarding the use of HPRT protein mutants as potential targets for therapeutic development.
اللغةen
الناشرElsevier
الموضوعHPRT1
Lesch–nyhan disease
Molecular dynamics simulation
Non-synonymous SNP
العنوانUnderstanding the structure-function relationship of HPRT1 missense mutations in association with Lesch-Nyhan disease and HPRT1-related gout by in silico mutational analysis.
النوعArticle
الصفحات161-171
رقم المجلد107
ESSN1879-0534
dc.accessType Abstract Only


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