Abstract
We have studied the structure and function of Human Misshapen / NIK-related kinase (MINK-1)through a combination of computational methods and experimental approaches,including (1)fold recognition and sequence-structure alignment for each structural domain using the threading program PROSPECT,(2)gene expression and protein-protein interaction analysis of yeast homologs of human MINK-1 domains,and (3)yeast two-hybrid screening for proteins that interact with human MINK-1.Our structure prediction dissects MINK-1 into four domains:a conserved N-terminal kinase domain,followed by a coiled-coil region and a proline-rich region,and a C- terminal GCK domain.Gene expression and yeast two-hybrid analysis of yeast homologs of the MINK-1 domains suggest that MINK-1 may be involved in cell-cycle progression and cytoskeletal control.Consistent with these predicted functions,our in-house yeast two-hybrid screen for proteins that interact with human MINK-1 provides strong evidence that the coiled-coil and proline-rich domains of MINK-1 participate in the regulation of cytoskeletal organization,cell-cycle control and apoptosis.A homology model of the MINK-1 kinase domain was used to screen the NCI open compound database in DOCK,and chemical compounds with pharmaceutically acceptable properties were identified.Further medicinal chemistry compound structure optimization and kinase assays are underway.
Keywords: mink, ste20-related kinases, gck domain, signal transduction, protein structure prediction, threading, yeast two-hybrid, gene expression, docking
Current Medicinal Chemistry
Title: Computational and Experimental Studies on Human Misshapen / NIK- Related Kinase MINK-1
Volume: 11 Issue: 5
Author(s): Kunbin Qu, Yanmei Lu, Nan Lin, Rajinder Singh, Xiang Xu, Donald G. Payan and Dong Xu
Affiliation:
Keywords: mink, ste20-related kinases, gck domain, signal transduction, protein structure prediction, threading, yeast two-hybrid, gene expression, docking
Abstract: We have studied the structure and function of Human Misshapen / NIK-related kinase (MINK-1)through a combination of computational methods and experimental approaches,including (1)fold recognition and sequence-structure alignment for each structural domain using the threading program PROSPECT,(2)gene expression and protein-protein interaction analysis of yeast homologs of human MINK-1 domains,and (3)yeast two-hybrid screening for proteins that interact with human MINK-1.Our structure prediction dissects MINK-1 into four domains:a conserved N-terminal kinase domain,followed by a coiled-coil region and a proline-rich region,and a C- terminal GCK domain.Gene expression and yeast two-hybrid analysis of yeast homologs of the MINK-1 domains suggest that MINK-1 may be involved in cell-cycle progression and cytoskeletal control.Consistent with these predicted functions,our in-house yeast two-hybrid screen for proteins that interact with human MINK-1 provides strong evidence that the coiled-coil and proline-rich domains of MINK-1 participate in the regulation of cytoskeletal organization,cell-cycle control and apoptosis.A homology model of the MINK-1 kinase domain was used to screen the NCI open compound database in DOCK,and chemical compounds with pharmaceutically acceptable properties were identified.Further medicinal chemistry compound structure optimization and kinase assays are underway.
Export Options
About this article
Cite this article as:
Qu Kunbin, Lu Yanmei, Lin Nan, Singh Rajinder, Xu Xiang, Payan G. Donald and Xu Dong, Computational and Experimental Studies on Human Misshapen / NIK- Related Kinase MINK-1, Current Medicinal Chemistry 2004; 11 (5) . https://dx.doi.org/10.2174/0929867043455873
DOI https://dx.doi.org/10.2174/0929867043455873 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
- Announcements
Related Articles
-
Disruption of Cell Death Signaling in Cancer: Impact on Disease Prognosis and Response to Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Advances in HTLV-1 Peptide Vaccines and Therapeutics
Current Protein & Peptide Science Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions
Current Signal Transduction Therapy Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications
Current Medicinal Chemistry Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations
Current Pharmaceutical Biotechnology Therapeutic AIDS Vaccines
Current Pharmaceutical Design Cathelicidins - Natures Attempt at Combinatorial Chemistry
Combinatorial Chemistry & High Throughput Screening Dietary Fatty Acids in Metabolic Syndrome, Diabetes and Cardiovascular Diseases
Current Diabetes Reviews Advances in Biologic Agents for the Treatment of Rheumatoid Arthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Development of Novel Protein Scaffolds as Alternatives to Whole Antibodies for Imaging and Therapy: Status on Discovery Research and Clinical Validation
Current Pharmaceutical Biotechnology Psoralen: A Biologically Important Coumarin with Emerging Applications
Mini-Reviews in Medicinal Chemistry Emerging Roles for Modulation of microRNA Signatures in Cancer Chemoprevention
Current Cancer Drug Targets Recent Advancement in Natural Hyaluronidase Inhibitors
Current Topics in Medicinal Chemistry Effectivity of Long Antigen Exposition Dendritic Cell Therapy (LANEXDC<sup>®</sup>) in the Palliative Treatment of Pancreatic Cancer
Current Medicinal Chemistry Aging and immunopathology in primary Sjögren's syndrome
Current Aging Science In Vitro and In Vivo Models for Analysis of Resistance to Anticancer Molecular Therapies
Current Medicinal Chemistry Insight to Pharmacokinetics of TKIs: Optimizing Practical Guidelines for Individualized Therapy
Current Drug Metabolism The Potential of Zn(II) N-Alkylpyridylporphyrins for Anticancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Overview of the Synthesis of Optically Active 3-Amino-2-Hydroxy-4-Phenylbutyric Acids, Key Intermediates for Numerous Bioactive Compounds
Mini-Reviews in Organic Chemistry Translational Multimodality Neuroimaging
Current Drug Targets