PMID: 7535923Mar 11, 1995Paper

Mutational sensitivity patterns define critical residues in the palm subdomain of the reverse transcriptase of human immunodeficiency virus type 1

Nucleic Acids Research
S F ChaoC A Hutchison

Abstract

We have analyzed 154 single amino acid replacement mutants within a 40 amino acid region (residues 164-203) of the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1). This region consists of two antiparallel beta-strands (strands 9 and 10) flanked by two alpha helices (E and F). The structure of this region of the 'palm' subdomain is conserved in a variety of DNA and RNA polymerases, indicating a critical role in enzyme structure and function. Functional assays were performed by screening RT activity of mutants expressed in E. coli. A functionally important region corresponding closely to beta-strands 9 and 10 and the loop joining them was revealed by its mutational sensitivity. Structural analysis of mutants was performed by using Western blots to assay correct folding, which is required for processing to produce the mature p66 and p51 RT species. This analysis indicates that beta-strand 10 is a structurally important region. Combined analysis of these two assays revealed diagnostic patterns of mutational sensitivity which identify key positions in the RT sequence at which a specific amino acid side chain is critical, either for structure or function, as well as residues which are external to the RT st...Continue Reading

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Citations

Feb 1, 2003·Journal of Molecular Biology·Gilda TachedjianStephen P Goff
Jan 12, 2001·AIDS Research and Human Retroviruses·J A WrobelC A Hutchison
Jul 10, 2004·AIDS Research and Human Retroviruses·James M SmithHarriet L Robinson
Jul 1, 1995·Antimicrobial Agents and Chemotherapy·P L Boyer, S H Hughes
Oct 25, 2003·Antimicrobial Agents and Chemotherapy·Karidia DialloM A Wainberg
Jul 3, 2013·PLoS Pathogens·Suzannah J RihnPaul D Bieniasz
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·J A WrobelC A Hutchison
Jan 1, 2015·PloS One·Elena CapelMiguel Angel Martinez
Jan 23, 2008·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Yaoxing HuangDavid D Ho
Jan 1, 1997·Canadian Journal of Microbiology·A RamezaniS Joshi

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