Atomistic details of effect of disulfide bond reduction on active site of Phytase B from <i>Aspergillus niger</i>: A MD Study

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Title	*Atomistic details of effect of disulfide bond reduction on active site of Phytase B from Aspergillus niger: A MD Study*
Authors	Kapil Kumar¹, Mudit Dixit², J M Khire¹ & Sourav Pal²*
Affiliation	¹NCIM, Biochemical Sciences Division, ²Electronic Structure Theory Group, Physical Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
Email	s.pal@ncl.res.in; *Corresponding author
Article Type	Hypothesis
Date	Received November 18, 2013; Accepted November 24, 2013; Published December 06, 2013
Abstract	The molecular integrity of the active site of phytases from fungi is critical for maintaining phytase function as efficient catalytic machines. In this study, the molecular dynamics (MD) of two monomers of phytase B from Aspergillus niger, the disulfide intact monomer (NAP) and a monomer with broken disulfide bonds (RAP), were simulated to explore the conformational basis of the loss of catalytic activity when disulfide bonds are broken. The simulations indicated that the overall secondary and tertiary structures of the two monomers were nearly identical but differed in some crucial secondary–structural elements in the vicinity of the disulfide bonds and catalytic site. Disulfide bonds stabilize the β-sheet that contains residue Arg66 of the active site and destabilize the α-helix that contains the catalytic residue Asp319. This stabilization and destabilization lead to changes in the shape of the active–site pocket. Functionally important hydrogen bonds and atomic fluctuations in the catalytic pocket change during the RAP simulation. None of the disulfide bonds are in or near the catalytic pocket but are most likely essential for maintaining the native conformation of the catalytic site.
Keywords	Phytase B; Active site integrity, Disulfide bonds, Thermostability, Molecular Dynamics Simulations, Protein folding.
Abbreviations	PhyB, 2.5 pH acid phophatese from Aspergillus niger; NAP, disulphide intact monomer of Phytase B; RAP, disulphide reduced monomer of Phytase B; Rg, radius of gyration; RMSD, root mean square deviation; MD, molecular dynamics.
Citation	Kumar et al. Bioinformation 9(19): 963-967 (2013)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.