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Multifunctional Transactivator of Transcription (Tat) Protein of Human Immunodeficiency Virus-1 as a Potential Drug Target

Vivek Darapaneni

Abstract


The HIV-1 transactivator of transcription (Tat) protein plays a pivotal role in the infectious lifecycle of human immunodeficiency virus-1. The objective of this study is to find the degree of conservation of the Tat protein and to detect conserved binding sites, which might be used as target sites for potential anti-Tat drugs. The conservation analysis was based on 3,365 amino acid sequences for Tat protein. The conservation analysis revealed a number of conserved and variable residues. The universally conserved residues identified in this study might be involved in either structure stabilizing or protein-protein interactions. The novel conserved residues which have been identified are Lys88, Lys89, Val91, Glu92, Glu94 and Thr95. Along with conservational analysis, structural analysis revealed novel binding sites, namely Cys22, Cys25, Cys27, Cys30, His33, Cys34, Cys37; Ile45, Lys51, Arg53, Gln54, Arg55; Gly44, Arg49, Lys50; Asp2, Val4, Ile8 and Met1, Pro3, Val4, Ile45, Tyr47, Lys50, Lys51, Arg52, Arg53. The outcome of this study provides the basis for developing anti-Tat drugs which have abridged potential to induce drug resistance through mutations.


Keywords


Tat protein; Conservation; Drugs; Mutation; Resistance; HIV-1; Binding sites

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