Computational analysis of PTP-1B site-directed mutations and their structural binding to potential inhibitors
DC Field | Value | Language |
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dc.contributor.author | Tasleem, Munazzah | - |
dc.contributor.author | Shoaib, Ambreen | - |
dc.contributor.author | Al-Shammary, Asma | - |
dc.contributor.author | Abdelgadir, Abdelmuhsin | - |
dc.contributor.author | El Asmar, Zeina | - |
dc.contributor.author | Jamal, Qazi Mohammad Sajid | - |
dc.contributor.author | Alrehaily, Abdulwahed | - |
dc.contributor.author | Bardcki, Fevzi | - |
dc.contributor.author | Sulieman, Abdel Moneim E. | - |
dc.contributor.author | Upadhyay, Tarun Kumar | - |
dc.contributor.author | Ansari, Irfan Ahmad | - |
dc.contributor.author | Lai, Dakun | - |
dc.contributor.author | Badraoui, Riadh | - |
dc.contributor.author | Yadav, Dharmendra Kumar | - |
dc.contributor.author | Saeed, Mohd | - |
dc.date.accessioned | 2023-01-19T01:41:40Z | - |
dc.date.available | 2023-01-19T01:41:40Z | - |
dc.date.created | 2023-01-18 | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 0145-5680 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86678 | - |
dc.description.abstract | Protein tyrosine phosphatase-1B (PTP-1B) is a well-known therapeutic target for diabetes and obesity as it suppresses insulin and leptin signaling. PTP-1B deletion or pharmacological suppression boosted glucose homeostasis and insulin signaling without altering hepatic fat storage. Inhibitors of PTP-1B may be useful in the treatment of type 2 diabetes, and shikonin, a naturally occurring naphthoquinone dye pigment, is reported to inhibit PTP-1B and possess antidiabetic properties. Since the cell contains a large number of phosphatases, PTP-1B inhibitors must be effective and selective. To explore more about the mechanism underlying the inhibitor's efficacy and selectivity, we investigated its top four pharmacophores and used site-directed mutagenesis to insert amino acid mutations into PTP-1B as an extension of our previous study where we identified 4 pharmacophores of shikonin. The study aimed to examine the site-directed mutations like R24Y, S215E, and S216C influence the binding of shikonin pharmacophores, which act as selective inhibitors of PTP-1B. To achieve this purpose, docking and molecular dynamics simulations of wild-type (WT) and mutant PTP-1B with antidiabetic compounds were undertaken. The simulation results revealed that site-directed mutations can change the hydrogen bond and hydrophobic interactions between shikonin pharmacophores and many residues in PTP-1B's active site, influencing the drug's binding affinity. These findings could aid researchers in better understanding PTP-1B inhibitors' selective binding mechanism and pave the path for the creation of effective PTP-1B inhibitors. (C) 2022 by the C.M.B. Association. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | C M B ASSOC | - |
dc.relation.isPartOf | CELLULAR AND MOLECULAR BIOLOGY | - |
dc.title | Computational analysis of PTP-1B site-directed mutations and their structural binding to potential inhibitors | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000898196800013 | - |
dc.identifier.doi | 10.14715/cmb/2022.68.7.13 | - |
dc.identifier.bibliographicCitation | CELLULAR AND MOLECULAR BIOLOGY, v.68, no.7, pp.75 - 84 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85143917720 | - |
dc.citation.endPage | 84 | - |
dc.citation.startPage | 75 | - |
dc.citation.title | CELLULAR AND MOLECULAR BIOLOGY | - |
dc.citation.volume | 68 | - |
dc.citation.number | 7 | - |
dc.contributor.affiliatedAuthor | Yadav, Dharmendra Kumar | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Multiple sequence alignment | - |
dc.subject.keywordAuthor | phylogenetic tree | - |
dc.subject.keywordAuthor | docking | - |
dc.subject.keywordAuthor | intra-molecular interactions | - |
dc.subject.keywordAuthor | site-directed mutagenesis | - |
dc.subject.keywordAuthor | stability | - |
dc.subject.keywordAuthor | MD simulation | - |
dc.subject.keywordPlus | HYDROGEN-BONDS | - |
dc.subject.keywordPlus | IN-SILICO | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | DERIVATIVES | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | OBESITY | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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