Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/xmlui/handle/123456789/21867
Title: Monomerization alters the dynamics of the lid region in Campylobacter jejuni CstII: an MD simulation study
Authors: PRABHAKAR, PK
SRIVASTAVA, A
RAO, KK
BALAJI, PV
Keywords: Dihydrofolate-Reductase
Molecular-Dynamics
Flexibility
Loop
Activation
Mechanism
Models
Issue Date: 2016
Publisher: TAYLOR & FRANCIS INC
Citation: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,34(4)778-791
Abstract: CstII, a bifunctional (alpha 2,3/8) sialyltransferase from Campylobacter jejuni, is a homotetramer. It has been reported that mutation of the interface residues Phe121 (F121D) or Tyr125 (Y125Q) leads to monomerization and partial loss of enzyme activity, without any change in the secondary or tertiary structures. MD simulations of both tetramer and monomer, with and without bound donor substrate, were performed for the two mutants and WT to understand the reasons for partial loss of activity due to monomerization since the active site is located within each monomer. RMSF values were found to correlate with the crystallographic B-factor values indicating that the simulations are able to capture the flexibility of the molecule effectively. There were no gross changes in either the secondary or tertiary structure of the proteins during MD simulations. However, interface is destabilized by the mutations, and more importantly the flexibility of the lid region (Gly152-Lys190) is affected. The lid region accesses three major conformations named as open, intermediate, and closed conformations. In both Y121Q and F121D mutants, the closed conformation is accessed predominantly. In this conformation, the catalytic base His188 is also displaced. Normal mode analysis also revealed differences in the lid movement in tetramer and monomer. This provides a possible explanation for the partial loss of enzyme activity in both interface mutants. The lid region controls the traffic of substrates and products in and out of the active site, and the dynamics of this region is regulated by tetramerization. Thus, this study provides valuable insights into the role of loop dynamics in enzyme activity of CstII.
URI: http://dx.doi.org/10.1080/07391102.2015.1054430
http://localhost:8080/xmlui/handle/123456789/21867
ISSN: 0739-1102
1538-0254
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