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Int. J. Mol. Sci. 2014, 15(3), 4221-4236; doi:10.3390/ijms15034221

Structure of N-Terminal Sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-Peptide with Phospholipase A2 from Venom of Andaman Cobra Sub-Species Naja naja sagittifera at 2.0 Å Resolution

1
Proteomics and Structural Biology Unit, Fundamental and Applied Biology Group, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia
2
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
3
Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
4
Gordon Life Science Institute, Boston, MA 02478, USA
*
Author to whom correspondence should be addressed.
Received: 16 January 2014 / Revised: 20 February 2014 / Accepted: 5 March 2014 / Published: 10 March 2014
(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)
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Abstract

Alzheimer’s disease (AD) is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ) are the prime player of AD’s neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2) in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer’s Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS) of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB) Code: 3JQ5). This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ–Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD. View Full-Text
Keywords: cobra venom; phospholipase A2; co-crystallization; Alzheimer’s disease; neuroinflammation; DAEFRHDS cobra venom; phospholipase A2; co-crystallization; Alzheimer’s disease; neuroinflammation; DAEFRHDS
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MDPI and ACS Style

Mirza, Z.; Pillai, V.G.; Zhong, W.-Z. Structure of N-Terminal Sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-Peptide with Phospholipase A2 from Venom of Andaman Cobra Sub-Species Naja naja sagittifera at 2.0 Å Resolution. Int. J. Mol. Sci. 2014, 15, 4221-4236.

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