The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations

Akubugwo Emmanuel I.; Okafor Irene N.; Ezebuo Fortunatus C.; Lukong Colin B.; Ifemeje Jonathan C.; Nwaka Andrew C.; Chilaka Ferdinand C.

doi:doi:10.11648/j.cbb.20160401.12

The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations

Akubugwo Emmanuel I., Okafor Irene N., Ezebuo Fortunatus C., Lukong Colin B., Ifemeje Jonathan C., Nwaka Andrew C., Chilaka Ferdinand C.

Published in Computational Biology and Bioinformatics (Volume 4, Issue 1)

Received: 18 January 2016 Accepted: 28 January 2016 Published: 17 February 2016

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Abstract

Snake venoms are rich in phospholipase A2 (PLA2) and their hydrolysis of cell membrane phospholipids explains the role of the enzyme in venom toxicity. Calcium is known to plays important role at the active site of PLA2 during catalysis. In this study, molecular dynamics simulations of free PLA2 and calcium bound PLA2 were carried out using GROMACS 4.5.5 to evaluate the role of calcium in PLA2 catalysis. The results showed that calcium induced formation of helical structures between Arg62 - Lys66, Asn107 - Tyr111 and Asp114 - Cys119 in PLA2 which with time disappeared through the formation and opening of loops. Calcium induced atomistic movements and conformational changes in snake venom PLA2 which led to the formation of a widened cleft at the active site of calcium bound PLA2 when compared with free PLA2. This could lead to a better binding and accommodation of substrate, thus enhancing catalysis. This study confirms the role of calcium towards the action of PLA2 in snake venom toxicity and could provide useful information for the design of small molecules that can function as PLA2 inhibitors.

Published in	Computational Biology and Bioinformatics (Volume 4, Issue 1)
DOI	10.11648/j.cbb.20160401.12
Page(s)	10-14
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2016. Published by Science Publishing Group

Keywords

Snake Venoms, Phospholipase A2, Calcium, Catalytic Site, Inhibitors of PLA2, Loop

References

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APA Style

Akubugwo Emmanuel I., Okafor Irene N., Ezebuo Fortunatus C., Lukong Colin B., Ifemeje Jonathan C., et al. (2016). The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Computational Biology and Bioinformatics, 4(1), 10-14. https://doi.org/10.11648/j.cbb.20160401.12

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ACS Style

Akubugwo Emmanuel I.; Okafor Irene N.; Ezebuo Fortunatus C.; Lukong Colin B.; Ifemeje Jonathan C., et al. The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Comput. Biol. Bioinform. 2016, 4(1), 10-14. doi: 10.11648/j.cbb.20160401.12

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AMA Style

Akubugwo Emmanuel I., Okafor Irene N., Ezebuo Fortunatus C., Lukong Colin B., Ifemeje Jonathan C., et al. The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Comput Biol Bioinform. 2016;4(1):10-14. doi: 10.11648/j.cbb.20160401.12

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@article{10.11648/j.cbb.20160401.12,
  author = {Akubugwo Emmanuel I. and Okafor Irene N. and Ezebuo Fortunatus C. and Lukong Colin B. and Ifemeje Jonathan C. and Nwaka Andrew C. and Chilaka Ferdinand C.},
  title = {The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations},
  journal = {Computational Biology and Bioinformatics},
  volume = {4},
  number = {1},
  pages = {10-14},
  doi = {10.11648/j.cbb.20160401.12},
  url = {https://doi.org/10.11648/j.cbb.20160401.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20160401.12},
  abstract = {Snake venoms are rich in phospholipase A2 (PLA2) and their hydrolysis of cell membrane phospholipids explains the role of the enzyme in venom toxicity. Calcium is known to plays important role at the active site of PLA2 during catalysis. In this study, molecular dynamics simulations of free PLA2 and calcium bound PLA2 were carried out using GROMACS 4.5.5 to evaluate the role of calcium in PLA2 catalysis. The results showed that calcium induced formation of helical structures between Arg62 - Lys66, Asn107 - Tyr111 and Asp114 - Cys119 in PLA2 which with time disappeared through the formation and opening of loops. Calcium induced atomistic movements and conformational changes in snake venom PLA2 which led to the formation of a widened cleft at the active site of calcium bound PLA2 when compared with free PLA2. This could lead to a better binding and accommodation of substrate, thus enhancing catalysis. This study confirms the role of calcium towards the action of PLA2 in snake venom toxicity and could provide useful information for the design of small molecules that can function as PLA2 inhibitors.},
 year = {2016}
}

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TY - JOUR
T1 - The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations
AU - Akubugwo Emmanuel I.
AU - Okafor Irene N.
AU - Ezebuo Fortunatus C.
AU - Lukong Colin B.
AU - Ifemeje Jonathan C.
AU - Nwaka Andrew C.
AU - Chilaka Ferdinand C.
Y1 - 2016/02/17
PY - 2016
N1 - https://doi.org/10.11648/j.cbb.20160401.12
DO - 10.11648/j.cbb.20160401.12
T2 - Computational Biology and Bioinformatics
JF - Computational Biology and Bioinformatics
JO - Computational Biology and Bioinformatics
SP - 10
EP - 14
PB - Science Publishing Group
SN - 2330-8281
UR - https://doi.org/10.11648/j.cbb.20160401.12
AB - Snake venoms are rich in phospholipase A2 (PLA2) and their hydrolysis of cell membrane phospholipids explains the role of the enzyme in venom toxicity. Calcium is known to plays important role at the active site of PLA2 during catalysis. In this study, molecular dynamics simulations of free PLA2 and calcium bound PLA2 were carried out using GROMACS 4.5.5 to evaluate the role of calcium in PLA2 catalysis. The results showed that calcium induced formation of helical structures between Arg62 - Lys66, Asn107 - Tyr111 and Asp114 - Cys119 in PLA2 which with time disappeared through the formation and opening of loops. Calcium induced atomistic movements and conformational changes in snake venom PLA2 which led to the formation of a widened cleft at the active site of calcium bound PLA2 when compared with free PLA2. This could lead to a better binding and accommodation of substrate, thus enhancing catalysis. This study confirms the role of calcium towards the action of PLA2 in snake venom toxicity and could provide useful information for the design of small molecules that can function as PLA2 inhibitors.
VL - 4
IS - 1
ER -

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Author Information

Akubugwo Emmanuel I.

Department of Biochemistry, Abia State University, Uturu, Nigeria
Okafor Irene N.

Department of Biochemistry, Faculty of Natural Sciences, Chukwuemeka Odumegwu Ojukwu University, Uli, Anambra State, Nigeria
Ezebuo Fortunatus C.

Department of Biochemistry, Faculty of Natural Sciences, Chukwuemeka Odumegwu Ojukwu University, Uli, Anambra State, Nigeria
Lukong Colin B.

Department of Biochemistry, Faculty of Natural Sciences, Chukwuemeka Odumegwu Ojukwu University, Uli, Anambra State, Nigeria
Ifemeje Jonathan C.

Department of Biochemistry, Faculty of Natural Sciences, Chukwuemeka Odumegwu Ojukwu University, Uli, Anambra State, Nigeria
Nwaka Andrew C.

Department of Biochemistry, Faculty of Natural Sciences, Chukwuemeka Odumegwu Ojukwu University, Uli, Anambra State, Nigeria
Chilaka Ferdinand C.

Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria

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Akubugwo Emmanuel I., Okafor Irene N., Ezebuo Fortunatus C., Lukong Colin B., Ifemeje Jonathan C., et al. (2016). The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Computational Biology and Bioinformatics, 4(1), 10-14. https://doi.org/10.11648/j.cbb.20160401.12

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ACS Style

Akubugwo Emmanuel I.; Okafor Irene N.; Ezebuo Fortunatus C.; Lukong Colin B.; Ifemeje Jonathan C., et al. The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Comput. Biol. Bioinform. 2016, 4(1), 10-14. doi: 10.11648/j.cbb.20160401.12

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AMA Style

Akubugwo Emmanuel I., Okafor Irene N., Ezebuo Fortunatus C., Lukong Colin B., Ifemeje Jonathan C., et al. The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations. Comput Biol Bioinform. 2016;4(1):10-14. doi: 10.11648/j.cbb.20160401.12

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@article{10.11648/j.cbb.20160401.12,
  author = {Akubugwo Emmanuel I. and Okafor Irene N. and Ezebuo Fortunatus C. and Lukong Colin B. and Ifemeje Jonathan C. and Nwaka Andrew C. and Chilaka Ferdinand C.},
  title = {The Role of Calcium on the Active Site of Snake Venom Phospholipase A2: Molecular Dynamics Simulations},
  journal = {Computational Biology and Bioinformatics},
  volume = {4},
  number = {1},
  pages = {10-14},
  doi = {10.11648/j.cbb.20160401.12},
  url = {https://doi.org/10.11648/j.cbb.20160401.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20160401.12},
  abstract = {Snake venoms are rich in phospholipase A2 (PLA2) and their hydrolysis of cell membrane phospholipids explains the role of the enzyme in venom toxicity. Calcium is known to plays important role at the active site of PLA2 during catalysis. In this study, molecular dynamics simulations of free PLA2 and calcium bound PLA2 were carried out using GROMACS 4.5.5 to evaluate the role of calcium in PLA2 catalysis. The results showed that calcium induced formation of helical structures between Arg62 - Lys66, Asn107 - Tyr111 and Asp114 - Cys119 in PLA2 which with time disappeared through the formation and opening of loops. Calcium induced atomistic movements and conformational changes in snake venom PLA2 which led to the formation of a widened cleft at the active site of calcium bound PLA2 when compared with free PLA2. This could lead to a better binding and accommodation of substrate, thus enhancing catalysis. This study confirms the role of calcium towards the action of PLA2 in snake venom toxicity and could provide useful information for the design of small molecules that can function as PLA2 inhibitors.},
 year = {2016}
}

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