Publications
Detailed Information
Ph-dependent structural dynamics of cathepsin d-family aspartic peptidase of clonorchis sinensis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Jung-Mi | - |
dc.contributor.author | Le, Huong Giang | - |
dc.contributor.author | Na, Byoung-Kuk | - |
dc.contributor.author | Yoo, Won Gi | - |
dc.date.accessioned | 2024-05-02T05:41:27Z | - |
dc.date.available | 2024-05-02T05:41:27Z | - |
dc.date.created | 2024-04-29 | - |
dc.date.created | 2024-04-29 | - |
dc.date.issued | 2021-09 | - |
dc.identifier.citation | Pathogens, Vol.10 No.9, p. 1128 | - |
dc.identifier.issn | 2076-0817 | - |
dc.identifier.uri | https://hdl.handle.net/10371/200454 | - |
dc.description.abstract | Cathepsin D (CatD; EC 3.4.23.5) family peptidases of parasitic organisms are regarded as potential drug targets as they play critical roles in the physiology and pathobiology of parasites. Previously, we characterized the biochemical features of cathepsin D isozyme 2 (CatD2) in the carcinogenic liver fluke Clonorchis sinensis (CsCatD2). In this study, we performed all-atomic molecular dynamics simulations by applying different systems for the ligand-free/bound forms under neutral and acidic conditions to investigate the pH-dependent structural alterations and associated functional changes in CsCatD2. CsCatD2 showed several distinctive characteristics as follows: (1) acidic pH caused major conformational transitions from open to closed state in this enzyme; (2) during 30-36-ns simulations, acidic pH contributed significantly to the formation of rigid beta-sheets around the catalytic residue Asp(219), higher occupancy (0% to 99%) of hydrogen bond than that of Asp(33), and enhanced stabilization of the CsCatD2-inhibtor complex; (3) neutral pH-induced displacement of the N-terminal part to hinder the accessibility of the active site and open allosteric site of this enzyme; and (4) the flap dynamics metrics, including distance (d(1)), TriC alpha angles (theta(1) and theta(2)), and dihedral angle (phi), account for the asymmetrical twisting motion of the active site of this enzyme. These findings provide an in-depth understanding of the pH-dependent structural dynamics of free and bound forms of CsCatD2 and basic information for the rational design of an inhibitor as a drug targeting parasitic CatD. | - |
dc.language | 영어 | - |
dc.publisher | MDPI AG | - |
dc.title | Ph-dependent structural dynamics of cathepsin d-family aspartic peptidase of clonorchis sinensis | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/pathogens10091128 | - |
dc.citation.journaltitle | Pathogens | - |
dc.identifier.wosid | 000701983300001 | - |
dc.identifier.scopusid | 2-s2.0-85114703217 | - |
dc.citation.number | 9 | - |
dc.citation.startpage | 1128 | - |
dc.citation.volume | 10 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Yoo, Won Gi | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | MOLECULAR-DYNAMICS | - |
dc.subject.keywordPlus | CYSTEINE PROTEASES | - |
dc.subject.keywordPlus | SERUM-PROTEINS | - |
dc.subject.keywordPlus | FLEXIBILITY | - |
dc.subject.keywordPlus | HEMOGLOBIN | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | SEQUENCE | - |
dc.subject.keywordPlus | ROLES | - |
dc.subject.keywordAuthor | Clonorchis sinensis | - |
dc.subject.keywordAuthor | cathepsin D | - |
dc.subject.keywordAuthor | aspartic peptidase | - |
dc.subject.keywordAuthor | molecular dynamics simulation | - |
dc.subject.keywordAuthor | pH effect | - |
dc.subject.keywordAuthor | flap dynamics | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.