Retroviral Integrase

From Proteopedia

proteopedia linkproteopedia link

Contents 1 Introduction 2 PFV Crystalization 3 Impact of Structure 4 Components 5 References

Introduction

Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism [responsible for strand-transfer inhibition action remain unclear] of action was not clear. On February 1st, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments. [However, Hare et al (2010) determined the structural constituents of retroviral integration. Further elucidation of the complete structure of the retroviral integrase, and its application to regulate functional and enzymatic activities could potentially enable researchers to delay the progression of, and provide the next best medical treatment for retroviral diseases.]

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.

PFV Crystalization

The remarkable stability of the IN-DNA complexes were determined by observing the "in vitro" strand transfer reactions, which were classified into three modes of deproteination migration: (1) single conserted, linearized target plasmid; (2) multiple concerted events, smear; (3) half-site events: open circular DNA. Further characterization of the PFV intasome also exhibited structural substantiality which implied strong protein-protein and protein-DNA interactions despite prolonged incubation under high ionic strength conditions.

Impact of Structure

Components

References

1.Stephen Hare, Saumya Shree Gupta1, Eugene Valkov1, Alan Engelman & Peter Cherepanov. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010/01/31/online Template:STRUCTURE 3l2q

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp