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From Recognition to Reaction Mechanism: An Overview on the Interactions between HIV-1 Protease and its Natural Targets

Author(s):

Monsurat M. Lawal, Zainab K. Sanusi, Thavendran Govender, Glenn E. M. Maguire, Bahareh Honarparvar and Hendrik G. Kruger*   Pages 1 - 34 ( 34 )

Abstract:


Current investigations of the human immunodeficiency virus protease (HIV-1 PR) as a druggable target towards the treatment of AIDS require an update to facilitate further development of promising inhibitors with improved inhibitory activities. For the past two decades, up to 100 scholarly reports appeared annually on the inhibition and catalytic mechanism of HIV-1 PR. A fundamental literature review on the prerequisite of HIV-1 PR action leading to the release of infectious virion is absent. Herein, recent advances (both computationally and experimentally) on the recognition mode and reaction mechanism of HIV-1 PR involving its natural targets is provided. This overview features more than 80 peer review articles from reputable journals. Recognition of the natural Gag and Gag-Pol cleavage junctions by this enzyme and its mutant analogues was first addressed. Thereafter, a comprehensive dissect of the enzymatic mechanism of HIV-1 PR on its natural polypeptide sequences from literature was put together. In addition, we highlighted ongoing research topics in which in silico methods could be harnessed to provide better insights on the catalytic mechanism of the HIV-1 protease in the presence of its natural substrates. Understanding the recognition and catalytic mechanism of HIV-1 PR leading to the release of an infective virion, which advertently affects the immune system, will assist in designing mechanism-based inhibitors with better bioactivity.

Keywords:

HIV-1 PR, Natural substrates, Recognition pattern, Reaction mechanism, Transition state modelling.

Affiliation:

Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041, Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041, Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041, Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041, Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041, Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4041



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