Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding

doi:10.5246/jcps.2012.01.004

Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding

Naheed Z Razwi, Rukhshan Khurshid, Mahjabeen Saleem^*, Sabiha Karim, Saeed Ahmad Nagra, Asmat Salim

1. Department of Biochemistry, CMH Lahore Medical College, Lahore, Pakistan
2. Fatima Jinnah Medical College, Lahore, Pakistan
3. Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan
4. College of Pharmacy, University of the Punjab, Lahore
5. Institute of Chemistry, University of the Punjab, Lahore, Pakistan
6. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, Karachi University, Pakistan

收稿日期:2011-06-27 修回日期:2011-10-15 出版日期:2012-01-01 发布日期:2012-01-01
通讯作者: Mahjabeen Saleem*

Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding

Naheed Z Razwi, Rukhshan Khurshid, Mahjabeen Saleem^*, Sabiha Karim, Saeed Ahmad Nagra, Asmat Salim

1. Department of Biochemistry, CMH Lahore Medical College, Lahore, Pakistan
2. Fatima Jinnah Medical College, Lahore, Pakistan
3. Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan
4. College of Pharmacy, University of the Punjab, Lahore
5. Institute of Chemistry, University of the Punjab, Lahore, Pakistan
6. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, Karachi University, Pakistan

Received:2011-06-27 Revised:2011-10-15 Online:2012-01-01 Published:2012-01-01
Contact: Mahjabeen Saleem*

摘要/Abstract

摘要： Apoptotic cell death plays an important role in the maintenance of the normal physiological state and in the pathogenesis of diseases. Granule exocytosis is the main pathway for the immune elimination of virus-infected cells and tumor cells by cytotoxic T lymphocytes and natural killer cells. In recent study, we have investigated the level of granzyme H in patients with breast cancer and in control subjects using enzymatic method. Our study also included the prediction of different sites of granzyme H that play a role in substrate and inhibitor recognition in apoptosis process by using 3D structural model of the enzyme. The research described the possible post-translational modification sites that may help the enzyme in immune elimination of tumor cells. Our study shows that the level of granzyme H was reduced in patients when compared to normal control subjects. There are a number of amino acids that function as substrate recognition sites in granzyme H. However, inhibitors may inhibit their activity and affect the process of autolysis.

关键词: Autolysis, Granzyme H, Apoptosis, Post translational modification

Abstract: Apoptotic cell death plays an important role in the maintenance of the normal physiological state and in the pathogenesis of diseases. Granule exocytosis is the main pathway for the immune elimination of virus-infected cells and tumor cells by cytotoxic T lymphocytes and natural killer cells. In recent study, we have investigated the level of granzyme H in patients with breast cancer and in control subjects using enzymatic method. Our study also included the prediction of different sites of granzyme H that play a role in substrate and inhibitor recognition in apoptosis process by using 3D structural model of the enzyme. The research described the possible post-translational modification sites that may help the enzyme in immune elimination of tumor cells. Our study shows that the level of granzyme H was reduced in patients when compared to normal control subjects. There are a number of amino acids that function as substrate recognition sites in granzyme H. However, inhibitors may inhibit their activity and affect the process of autolysis.

Key words: Autolysis, Granzyme H, Apoptosis, Post translational modification

中图分类号:

R915

Supporting: ^*Corresponding author. Tel.: 97-42-9230355

Naheed Z Razwi, Rukhshan Khurshid, Mahjabeen Saleem^*, Sabiha Karim, Saeed Ahmad Nagra, Asmat Salim. Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding[J]. , DOI: 10.5246/jcps.2012.01.004.

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Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding

Biochemical analysis of granzyme H and elucidation of its structurally important residues involved in substrate and inhibitor binding

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