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Molecular Biology Reports

, Volume 38, Issue 5, pp 2953–2960 | Cite as

Granzyme M: characterization with sites of post-translational modification and specific sites of interaction with substrates and inhibitors

  • Rukhshan Khurshid
  • Mahjabeen SaleemEmail author
  • Muhammad Saleem Akhtar
  • Asmat Salim
Article

Abstract

Granzymes kill cells in a variety of ways. They induce mitochondrial dysfunction through caspase dependent and caspase-independent pathways and destroy DNA and the integrity of the nucleus. For gaining a better understanding of the molecular function of granzyme M and its NK cell specificity, structural characterization of this enzyme by molecular modeling as well as its detailed comparison with other granzymes is presented in this study. The study includes mode of action of granzyme M using cationic binding sites, substrate specificity, post-translational structural modification and its functional relationship and interaction of the enzyme with inhibitor in an attempt to explore how the activity of human granzyme M is controlled under physiological conditions. It is concluded from the present study that the post-translational modification, including Oglycosylation of serine, phosphorylation of serine and threonine and myristoylation of glycine, play an important role in the interaction of enzyme with the cell surface membrane and regulate protein trafficking and stability. Phosphorylated serine and threonine also plays a role in tumor elimination, viral clearance and tissue repair. In Gzm M there are cationic sites, cs1 and cs2 that may participate in binding of Gzm M to the cell surface, thereby promoting its uptake and eventual release into the cytoplasm. Gzm M shows apoptotic activity both by caspase dependent and independent pathways. Modeling of inhibitors bound to the granzyme active site shows that the dimer also contributes to substrate specificity in a unique manner by extending the active-site cleft.

Keywords

Gzm M Apoptosis Post-translational modification Inhibitor 

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Rukhshan Khurshid
    • 1
  • Mahjabeen Saleem
    • 2
    Email author
  • Muhammad Saleem Akhtar
    • 3
  • Asmat Salim
    • 4
  1. 1.Department of BiochemistryFatima Jinnah Medical CollegeLahorePakistan
  2. 2.Institute of Biochemistry and BiotechnologyUniversity of the PunjabLahorePakistan
  3. 3.Department of ChemistryGovt. Islamia CollegeLahorePakistan
  4. 4.Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan

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