Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKarmakar, Tarak
dc.contributor.authorRoy, Sourav
dc.contributor.authorBalaram, Hemalatha
dc.contributor.authorBalasubramanian, Sundaram
dc.identifier.citationKarmakar, T.; Roy, S.; Balaram, H.; Balasubramanian, S., Structural and dynamical correlations in PfHGXPRT oligomers: A molecular dynamics simulation study. Journal of Biomolecular Structure & Dynamics 2016, 34 (7), 1590-1605
dc.identifier.citationJournal of Biomolecular Structure & Dynamicsen_US
dc.descriptionRestricted Accessen_US
dc.description.abstractPfHGXPRT is a key enzyme involved in purine nucleotide salvage pathway of the malarial parasite, Plasmodium falciparum. Atomistic molecular dynamics simulations have been performed on two types of PfHGXPRT dimers (D1 and D3) and its tetramer in their apo and ligand-bound states. A significant event in the catalytic cycle is the dynamics of a gate that provides access for the ligand molecules to the reaction center. The gate is formed by loops II and IV, the former being the most flexible. Large amplitude conformational changes have been observed in active site loop II. Upon complete occupancy of the active site, loop II gets stabilized due to specific interactions between its residues and the ligand molecules. Remote loop, X, is seen to be less fluxional in the D3 dimer than in D1 which is rationalized as due to the greater number of inter-subunit contacts in the former. The presence of ligand molecules in subunits of the tetramer further reduces the flexibility of loop X epitomizing a communication between this region and the active sites in the tetramer. These observations are in accordance with the outcomes of several experimental investigations. Participation of loop X in the oligomerization process has also been discerned. Between the two types of dimers in solution, D1 tetramerizes readily and thus would not be present as free dimers. We conjecture an equilibrium to exist between D3 and the tetramer in solution; upon binding of the ligand molecules to the D3 dimer, this equilibrium shifts toward the tetramer.en_US
dc.publisherTaylor & Francis Incen_US
dc.rights@Taylor & Francis Inc, 2016en_US
dc.subjectBiochemistry & Molecular Biologyen_US
dc.subjectloop openingen_US
dc.subjectremote loopen_US
dc.subjectinter-subunit interactionsen_US
dc.subjectHypoxanthine-Guanine Phosphoribosyltransferaseen_US
dc.subjectAcyclic Nucleoside Phosphonatesen_US
dc.subjectState Analog Inhibitoren_US
dc.subjectNormal Mode Refinementen_US
dc.subject2.0 Angstrom Structureen_US
dc.subjectXanthine Phosphoribosyltransferaseen_US
dc.subject6-Oxopurine Phosphoribosyltransferasesen_US
dc.titleStructural and dynamical correlations in PfHGXPRT oligomers: A molecular dynamics simulation studyen_US
Appears in Collections:Research Articles (Balasubramanian Sundaram)
Research Papers (Hemalatha Balaram)

Files in This Item:
File Description SizeFormat 
  Restricted Access
2.11 MBAdobe PDFView/Open Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.