Academic Journal
Mapping increased flexibility and conformational divergence via N-terminal helix-to-coil transition in USP12 mutant Y49N: a comprehensive in-detail normal mode simulation study.
| Τίτλος: | Mapping increased flexibility and conformational divergence via N-terminal helix-to-coil transition in USP12 mutant Y49N: a comprehensive in-detail normal mode simulation study. |
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| Συγγραφείς: | Bhattacharya I; Amity Institute of Biotechnology, Amity University, Kolkata, W.B., India., Paul I; Amity Institute of Biotechnology, Amity University, Kolkata, W.B., India., Saha M; Amity Institute of Biotechnology, Amity University, Kolkata, W.B., India.; Department of Zoology, Seth Anandram Jaipuria College, Kolkata, W.B., India., Ray S; Amity Institute of Biotechnology, Amity University, Kolkata, W.B., India. raysujay@gmail.com. |
| Πηγή: | Journal of biological physics [J Biol Phys] 2026 Jun 26; Vol. 52 (1). Date of Electronic Publication: 2026 Jun 26. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Kluwer Country of Publication: Netherlands NLM ID: 0417731 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-0689 (Electronic) Linking ISSN: 00920606 NLM ISO Abbreviation: J Biol Phys Subsets: MEDLINE |
| Imprint Name(s): | Publication: Dordrecht : Kluwer Original Publication: Blacksburg, Va., University Publications. |
| Ιατρικοί όροι (MeSH): | Ubiquitin Thiolesterase*/chemistry , Ubiquitin Thiolesterase*/genetics , Mutant Proteins*/chemistry , Mutant Proteins*/genetics , Mutation* , Molecular Dynamics Simulation*, Humans ; Models, Molecular ; Amino Acid Sequence ; Protein Conformation |
| Περίληψη: | The family of deubiquitinating enzymes is primarily involved in the removal of ubiquitin chains from specific target proteins. Among these proteins, ubiquitin-specific protease 12 (USP12 protein) has been identified as a key molecule in regulating cellular homeostasis, cancer progression, and immune regulation. This protein is reportedly associated with colorectal cancer, prostate cancer, and breast cancer, along with neurodegenerative disorders like Huntington's disease. The study of mutations in USP12 could be crucial for understanding its impact on cancer and neurodegeneration, making it a potential target for therapeutics against such diseases. Our study uses a sequence-based and a structure-based screening method to identify a mutation in USP12 having the most deleterious and destabilizing effect. The mutation Y49N was found to significantly alter structural and biological functions of USP12 protein while compromising its stability. A total of 5000 conformations were generated for wild-type and Y49N_USP12 structures through normal mode analysis and a comparative study was conducted. We evaluated parameters like RMSD and R (© 2026. The Author(s), under exclusive licence to Springer Nature B.V.) |
| Competing Interests: | Declarations. Conflict of interest: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Conformational divergence; Helix-to-coil; Mutational screening; Normal mode simulation; USP12 |
| Substance Nomenclature: | EC 3.4.19.12 (Ubiquitin Thiolesterase) 0 (USP12 protein, human) 0 (Mutant Proteins) |
| Entry Date(s): | Date Created: 20260625 Date Completed: 20260626 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13304049 |
| DOI: | 10.1007/s10867-026-09717-w |
| PMID: | 42350869 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-0689 |
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| DOI: | 10.1007/s10867-026-09717-w |