Skip to main content
  • Poster presentation
  • Open access
  • Published:

N-myristoyltransferase1 and N-myristoyltransferase2 Exhibit Differential Substrate Specificity for HIV-Gag and HIV-Nef

Background

N-terminal myristoylation of Gag and Nef plays a critical role in retroviral virulence and budding of newly formed particles. Myristoylation involves the transfer of a myristate moiety from myristoyl-CoenzymeA (myristoyl-CoA) to substrate proteins such as Gag and Nef. Two isozymes accomplish this process in humans, and are known as N-myristoyltransferase1 (NMT1) and N-myristoyltransferase2 (NMT2). We used a biochemical approach to determine myristoylation kinetics for Gag and Nef as well as preferential substrate specificity for NMT1 or NMT2.

Materials and methods

NBD-labeled peptides containing the myristoylation sequence for Gag or Nef were myristoylated by recombinant NMT1 or NMT2 and subsequently analyzed by HPLC analysis.

Results

Results of the kinetics studies (Km, Kcat, catalytic efficiency, turnover number, etc.) indicate that both isozymes prefer Nef up to 150 times vs. Gag as a substrate. Both isozymes also exhibit greater catalytic efficiency in myristoylating Nef. Interestingly, Nef is preferentially myristoylated when Gag is present in the system.

Conclusion

This study is the first report of a differential role of NMT1 and NMT2 in the myristoylation of retroviral proteins and provides a new target in the treatment of HIV.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kelly Seaton.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Seaton, K., Smith, C. N-myristoyltransferase1 and N-myristoyltransferase2 Exhibit Differential Substrate Specificity for HIV-Gag and HIV-Nef. Retrovirology 2 (Suppl 1), P88 (2005). https://doi.org/10.1186/1742-4690-2-S1-P88

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1742-4690-2-S1-P88

Keywords