Abstract
The hydrophobic core in Bcl-xL composed of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 is highly conserved and essential for protein folding, protein stability and binding affinity with BH3-peptide. 9 mutants of Ile140 residue were constructed and characterized in order to get better understanding of the effect of the hydrophobic core. Binding assay demonstrated that binding affinities between 4 charged mutants and BH3-peptide were significantly weakened or lost, suggesting that the integrity of the hydrophobic core has close relationship with binding. The CD spectroscopy results indicated that disruption of the hydrophobic core may affect local conformation within the protein and result in intrinsic inactivity. Further chemical-induced protein folding results on these 4 mutants revealed that the conserved hydrophobic core is also important for the protein stability.
Keywords: Bad-BH3, Bcl-xL, binding, hydrophobic core, site-directed mutagenesis, stability
Protein & Peptide Letters
Title:Site-directed Mutagenesis Study of the Ile140 in Conserved Hydrophobic Core of Bcl-xL
Volume: 19 Issue: 9
Author(s): Xin Zhang, Ying Tan, Rui Zhao, Bizhu Chu, Chunyan Tan and Yuyang Jiang
Affiliation:
Keywords: Bad-BH3, Bcl-xL, binding, hydrophobic core, site-directed mutagenesis, stability
Abstract: The hydrophobic core in Bcl-xL composed of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 is highly conserved and essential for protein folding, protein stability and binding affinity with BH3-peptide. 9 mutants of Ile140 residue were constructed and characterized in order to get better understanding of the effect of the hydrophobic core. Binding assay demonstrated that binding affinities between 4 charged mutants and BH3-peptide were significantly weakened or lost, suggesting that the integrity of the hydrophobic core has close relationship with binding. The CD spectroscopy results indicated that disruption of the hydrophobic core may affect local conformation within the protein and result in intrinsic inactivity. Further chemical-induced protein folding results on these 4 mutants revealed that the conserved hydrophobic core is also important for the protein stability.
Export Options
About this article
Cite this article as:
Zhang Xin, Tan Ying, Zhao Rui, Chu Bizhu, Tan Chunyan and Jiang Yuyang, Site-directed Mutagenesis Study of the Ile140 in Conserved Hydrophobic Core of Bcl-xL, Protein & Peptide Letters 2012; 19 (9) . https://dx.doi.org/10.2174/092986612802084500
DOI https://dx.doi.org/10.2174/092986612802084500 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
In Vivo Treatment Efficacy of Essential Oil Isolated from Seeds of <i>Momordica charantia</i> in Streptozotocin-Induced Diabetes Mellitus
Recent Patents on Biotechnology Synthesis and Preliminary Anti-HIV Activities of Andrographolide Derivatives
Medicinal Chemistry Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Deubiquitinating Enzymes as Promising Drug Targets for Infectious Diseases
Current Pharmaceutical Design Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease
Current Alzheimer Research The Role of YY1 in Oncogenesis and Its Potential as a Drug Target in Cancer Therapies
Current Cancer Drug Targets The Potential and Limitations of p38MAPK as a Drug Target for the Treatment of Hematological Malignancies
Current Drug Targets Artemisia Species as a New Candidate for Diabetes Therapy: A Comprehensive Review
Current Molecular Medicine Design, Synthesis and Antiproliferative Activity of 2-Acetamidothiazole-5- carboxamide Derivatives
Medicinal Chemistry Development ofNovel Compounds to Treat Autoimmune and Inflammatory Diseases and Graft Versus Host Reactions
Endocrine, Metabolic & Immune Disorders - Drug Targets Inducers of Heme Oxygenase-1
Current Pharmaceutical Design Structure-Function Relationships and Clinical Applications of L-Asparaginases
Current Medicinal Chemistry Releasing of Herpes Simplex Virus Carrying NGF in Subarachnoid Space Promotes the Functional Repair in Spinal Cord Injured Rats
Current Gene Therapy Studies of NVP-BEZ235 in Melanoma
Current Cancer Drug Targets mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems
Current Drug Targets Histone Deacetylase Inhibitors in the Treatment of Hematological Malignancies
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic: Mechanisms of Drug Sensitivity and Resistance in Cancer (Guest Editor: Lorraine ODriscoll)]
Current Cancer Drug Targets Recent Approaches to Improve the Antitumor Efficacy of Temozolomide
Current Medicinal Chemistry Mikuliczs Disease and its Extraglandular Lesions
Current Immunology Reviews (Discontinued) Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials
Current Cancer Drug Targets