Abstract
Viral DNA integration into the infected cell genome is an essential step in the HIV-1 life cycle. Hence, the viral integrase enzyme has become an important target for antiviral therapy. The integrase's activity action relies on the binding to its cellular partners, therefore the knowledge of the structural determinants is very important from a therapeutic perspective. Here we first review published computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein. Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein's mutations which impair protein function and HIV-1 virus replication in vivo without significantly affecting enzymatic activity.
Keywords: HIV-1 integrase, human Pin1, protein – protein interaction, class II mutant.
Current Pharmaceutical Design
Title:HIV-1 Integrase Binding to its Cellular Partners: A Perspective from Computational Biology
Volume: 20 Issue: 21
Author(s): Vo Cam Quy, Vincenzo Carnevale, Lara Manganaro, Marina Lusic, Giulia Rossetti, Vanessa Leone, Cristina Fenollar-Ferrer, Simone Raugei, Giannino Del Sal, Mauro Giacca and Paolo Carloni
Affiliation:
Keywords: HIV-1 integrase, human Pin1, protein – protein interaction, class II mutant.
Abstract: Viral DNA integration into the infected cell genome is an essential step in the HIV-1 life cycle. Hence, the viral integrase enzyme has become an important target for antiviral therapy. The integrase's activity action relies on the binding to its cellular partners, therefore the knowledge of the structural determinants is very important from a therapeutic perspective. Here we first review published computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein. Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein's mutations which impair protein function and HIV-1 virus replication in vivo without significantly affecting enzymatic activity.
Export Options
About this article
Cite this article as:
Quy Cam Vo, Carnevale Vincenzo, Manganaro Lara, Lusic Marina, Rossetti Giulia, Leone Vanessa, Fenollar-Ferrer Cristina, Raugei Simone, Sal Del Giannino, Giacca Mauro and Carloni Paolo, HIV-1 Integrase Binding to its Cellular Partners: A Perspective from Computational Biology, Current Pharmaceutical Design 2014; 20 (21) . https://dx.doi.org/10.2174/13816128113199990631
DOI https://dx.doi.org/10.2174/13816128113199990631 |
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
-
Phytoecdysteroids - From Isolation to Their Effects on Humans
Current Medicinal Chemistry Senescence and Cell Death Pathways and Their Role in Cancer Therapeutic Outcome
Current Medicinal Chemistry Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application
Current Gene Therapy Epothilone B and its Analogs - A New Family of Anticancer Agents
Mini-Reviews in Medicinal Chemistry Writers and Erasers of Histone Lysine methylation with Clinically Applied Modulators: Promising Target for Cancer Therapy
Current Pharmaceutical Design PI3K-Akt Signaling and Viral Infection
Recent Patents on Biotechnology Recent Progress on Tumor Missile Therapy and Tumor Vascular Targeting Therapy as a New Approach
Current Vascular Pharmacology An Update on Overcoming MDR1-Mediated Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Design Reprogramming Cancer Cells in Endocrine-Related Tumors: Open Issues
Current Medicinal Chemistry Receptor Tyrosine Kinases as Target for Anti-Cancer Therapy
Current Pharmaceutical Design Bortezomib – First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery P-glycoprotein as a Drug Target in the Treatment of Multidrug Resistant Cancer
Current Drug Targets Local Gene Delivery for Cancer Therapy
Current Gene Therapy MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Cardiac Disease
Recent Patents on Biomarkers ANTI-ADHESION Evolves To a Promising Therapeutic Concept in Oncology
Current Medicinal Chemistry DMBA- Induced Breast Cancer: A Hormonal Camouflage
Current Cancer Therapy Reviews An Overview on Pyranocoumarins: Synthesis and Biological Activities
Current Organic Chemistry Peptide-Receptor Ligands and Multivalent Approach
Anti-Cancer Agents in Medicinal Chemistry Possible Pathways of Hepatotoxicity Caused by Chemical Agents
Current Drug Metabolism Roles of p97-Associated Deubiquitinases in Protein Quality Control at the Endoplasmic Reticulum
Current Protein & Peptide Science