Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Dong-Gyun | - |
dc.contributor.author | Cho, Sujin | - |
dc.contributor.author | Lee, Kyu-Yeon | - |
dc.contributor.author | Cheon, Seung-Ho | - |
dc.contributor.author | Yoon, Hye-Jin | - |
dc.contributor.author | Lee, Joo-Youn | - |
dc.contributor.author | Kim, Dongyoon | - |
dc.contributor.author | Shin, Kwang-Soo | - |
dc.contributor.author | Koh, Choong-Hyun | - |
dc.contributor.author | Koo, Ji Sung | - |
dc.contributor.author | Choi, Yuri | - |
dc.contributor.author | Lee, Hyung Ho | - |
dc.contributor.author | Oh, Yu-Kyoung | - |
dc.contributor.author | Jeong, Yoo-Seong | - |
dc.contributor.author | Chung, Suk-Jae | - |
dc.contributor.author | Baek, Moonkyu | - |
dc.contributor.author | Jung, Kwan-Young | - |
dc.contributor.author | Lim, Hyo Jin | - |
dc.contributor.author | Kim, Hyoun Sook | - |
dc.contributor.author | Park, Sung Jean | - |
dc.contributor.author | Lee, Jeong-Yeon | - |
dc.contributor.author | Lee, Sang Jae | - |
dc.contributor.author | Lee, Bong-Jin | - |
dc.date.accessioned | 2022-07-07T01:42:56Z | - |
dc.date.available | 2022-07-07T01:42:56Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2021-01 | - |
dc.identifier.issn | 1420-682X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/142507 | - |
dc.description.abstract | NAD(P)-dependent steroid dehydrogenase-like (NSDHL), an essential enzyme in human cholesterol synthesis and a regulator of epidermal growth factor receptor (EGFR) trafficking pathways, has attracted interest as a therapeutic target due to its crucial relevance to cholesterol-related diseases and carcinomas. However, the development of pharmacological agents for targeting NSDHL has been hindered by the absence of the atomic details of NSDHL. In this study, we reported two X-ray crystal structures of human NSDHL, which revealed a detailed description of the coenzyme-binding site and the unique conformational change upon the binding of a coenzyme. A structure-based virtual screening and biochemical evaluation were performed and identified a novel inhibitor for NSDHL harboring suppressive activity towards EGFR. In EGFR-driven human cancer cells, treatment with the potent NSDHL inhibitor enhanced the antitumor effect of an EGFR kinase inhibitor. Overall, these findings could serve as good platforms for the development of therapeutic agents against NSDHL-related diseases. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER BASEL AG | - |
dc.title | Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Jeong-Yeon | - |
dc.identifier.doi | 10.1007/s00018-020-03490-2 | - |
dc.identifier.scopusid | 2-s2.0-85080991903 | - |
dc.identifier.wosid | 000561619300002 | - |
dc.identifier.bibliographicCitation | CELLULAR AND MOLECULAR LIFE SCIENCES, v.78, no.1, pp.207 - 225 | - |
dc.relation.isPartOf | CELLULAR AND MOLECULAR LIFE SCIENCES | - |
dc.citation.title | CELLULAR AND MOLECULAR LIFE SCIENCES | - |
dc.citation.volume | 78 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 207 | - |
dc.citation.endPage | 225 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | BIOSYNTHESIS | - |
dc.subject.keywordPlus | ENZYMES | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | DEHYDROGENASE | - |
dc.subject.keywordPlus | VALIDATION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | GENES | - |
dc.subject.keywordAuthor | NSDHL | - |
dc.subject.keywordAuthor | Cholesterol synthesis pathway | - |
dc.subject.keywordAuthor | Membrane-anchored protein | - |
dc.subject.keywordAuthor | Structure-based drug design | - |
dc.subject.keywordAuthor | EGFR | - |
dc.identifier.url | https://link.springer.com/article/10.1007%2Fs00018-020-03490-2 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.