Monomerization alters the dynamics of the lid region in Campylobacter jejuni CstII: an MD simulation study
| Autor: | Petety V. Balaji, K. Krishnamurthy Rao, Alka Srivastava, Pradeep Kumar Prabhakar |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Models Molecular 030103 biophysics Sialyltransferase Protein Conformation Open Conformation Activation Plasma protein binding Molecular Dynamics Simulation Closed conformation medicine.disease_cause Closed Conformation Campylobacter jejuni 03 medical and health sciences Structure-Activity Relationship Protein structure Conformer Population Structural Biology Models medicine Oligomerization Protein Interaction Domains and Motifs Molecular Biology Mutation Molecular-Dynamics biology Chemistry Hydrogen Bonding General Medicine Lid Dynamics biology.organism_classification Molecular biology Protein multimerization Sialyltransferases Protein Subunits 030104 developmental biology Biochemistry biology.protein Dihydrofolate-Reductase Mechanism Flexibility Loop Protein Multimerization Homotetramer Protein Binding |
| Zdroj: | Journal of biomolecular structuredynamics. 34(4) |
| ISSN: | 1538-0254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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