Abstract
Matrix Metalloproteinases (MMPs) are zinc-containing proteinases that are responsible for the metabolism of extracellular matrix proteins. Overexpression of MMPs has been associated with a wide range of pathological diseases such as arthritis, cancer, multiple sclerosis and Alzheimers disease. The excessive and unregulated activity of Matrix Metalloproteinases type 2 (MMP-2), also known as gelatinase A, has been identified in a numbers of cancer metastases. Several MMP inhibitors (MMPi) have been proposed in the literature aiming to interfere in the MMPs activity. In this work we performed long MD simulations in order to study the dynamical behavior of the binding pocket S1 in the apo forms of MMP type 2 and 3, and identify, at the molecular level, the structural properties relevant for the designing of specific inhibitor of MMP-2.
Keywords: Matrix metalloproteinse, molecular dynamics, S1' binding pocket, MMP-2, MMP-3, metalloproteinase inhibitor
Current Pharmaceutical Design
Title: Molecular Dynamics Simulations of Metalloproteinases Types 2 and 3 Reveal Differences in the Dynamic Behavior of the S1 Binding Pocket
Volume: 13 Issue: 34
Author(s): Cesar Augusto F. de Oliveira, Maurice Zissen, John Mongon and J. Andrew Mccammon
Affiliation:
Keywords: Matrix metalloproteinse, molecular dynamics, S1' binding pocket, MMP-2, MMP-3, metalloproteinase inhibitor
Abstract: Matrix Metalloproteinases (MMPs) are zinc-containing proteinases that are responsible for the metabolism of extracellular matrix proteins. Overexpression of MMPs has been associated with a wide range of pathological diseases such as arthritis, cancer, multiple sclerosis and Alzheimers disease. The excessive and unregulated activity of Matrix Metalloproteinases type 2 (MMP-2), also known as gelatinase A, has been identified in a numbers of cancer metastases. Several MMP inhibitors (MMPi) have been proposed in the literature aiming to interfere in the MMPs activity. In this work we performed long MD simulations in order to study the dynamical behavior of the binding pocket S1 in the apo forms of MMP type 2 and 3, and identify, at the molecular level, the structural properties relevant for the designing of specific inhibitor of MMP-2.
Export Options
About this article
Cite this article as:
de Oliveira F. Cesar Augusto, Zissen Maurice, Mongon John and Mccammon Andrew J., Molecular Dynamics Simulations of Metalloproteinases Types 2 and 3 Reveal Differences in the Dynamic Behavior of the S1 Binding Pocket, Current Pharmaceutical Design 2007; 13 (34) . https://dx.doi.org/10.2174/138161207782794211
DOI https://dx.doi.org/10.2174/138161207782794211 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Radiolabelled Peptides: Eon in Radiopharmaceutical
Current Radiopharmaceuticals Recent Advances in the Chemistry and Biology of Folypoly-γ-glutamate Synthetase Substrates and Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents SPECT-CT and PET-CT in Oncology - An Overview
Current Medical Imaging The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy
Current Drug Targets Editorial (Thematic Issue: “miRNA and Cancer; Computational and Experimental Approaches”)
Current Pharmaceutical Biotechnology Cellular Senescence in the Development and Treatment of Cancer
Current Pharmaceutical Design Players in ADP-ribosylation: Readers and Erasers
Current Protein & Peptide Science Developing Stress Assessment forms for Thai Cancer Patients: The Thai Version of the Modified Symptoms of Stress Inventory (Modified SOSI)
Current Psychiatry Research and Reviews Anticancer Activity and Anti-inflammatory Studies of 5-Aryl-1,4-benzodiazepine Derivatives
Anti-Cancer Agents in Medicinal Chemistry Mucosal Healing in Ulcerative Colitis: Where do we Stand?
Current Drug Targets New Developments of Differentiation Therapy of Acute Myeloid Leukemia
Current Pharmacogenomics and Personalized Medicine CRM1-Mediated Nuclear Export of Proteins and Drug Resistance in Cancer
Current Medicinal Chemistry The Role of Trophoblast Nutrient and Ion Transporters in the Development of Pregnancy Complications and Adult Disease
Current Vascular Pharmacology Glycation and Hypoxia: Two Key Factors for Adipose Tissue Dysfunction
Current Medicinal Chemistry Synergistic Interaction of Telomerase-Specific Oncolytic Virotherapy and Chemotherapeutic Agents for Human Cancer
Current Pharmaceutical Biotechnology Betulinic Acid as a Potent and Complex Antitumor Phytochemical: A Minireview
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Polycomb Targeting in Human Cancer
Recent Patents on Regenerative Medicine Electroporation Advances in Large Animals
Current Gene Therapy Circular RNAs and Glioma: Small Molecule with Big Actions
Current Molecular Medicine Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic
Current Cancer Drug Targets