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dc.contributor.authorRoy, Sourav
dc.contributor.authorKarmakar, Tarak
dc.contributor.authorRao, Vasudeva S. Prahlada
dc.contributor.authorNagappa, Lakshmeesha K.
dc.contributor.authorBalasubramanian, Sundaram
dc.contributor.authorBalaram, Hemalatha
dc.date.accessioned2016-10-17T10:54:00Z-
dc.date.available2016-10-17T10:54:00Z-
dc.date.issued2015
dc.identifier.citationMolecular Biosystemsen_US
dc.identifier.citation11en_US
dc.identifier.citation5en_US
dc.identifier.citationRoy, S.; Karmakar, T.; Rao, V. S. P.; Nagappa, L. K.; Balasubramanian, S.; Balaram, H., Slow ligand-induced conformational switch increases the catalytic rate in Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferase. Molecular Biosystems 2015, 11 (5), 1410-1424.en_US
dc.identifier.issn1742-206X
dc.identifier.urihttp://hdl.handle.net/10572/1869-
dc.descriptionRestricted accessen_US
dc.description.abstractP. falciparum (Pf) hypoxanthine guanine xanthine phosphoribosyltransferase (HGXPRT) exhibits a unique mechanism of activation where the enzyme switches from a low activity (unactivated) to a high activity (activated) state upon pre-incubation with substrate/products. Xanthine phosphoribosylation by unactivated PfHGXPRT exhibits a lag phase, the duration of which reduces with an increase in concentration of the enzyme or substrate, PRPP center dot Mg2+. Activated PfHGXPRT does not display the lag phase and exhibits a ten-fold drop in the Km value for PRPP center dot Mg2+. These observations suggest the involvement of ligand-mediated oligomerization and conformational changes in the process of activation. The dipeptide Leu-Lys in the PPi binding site of human and T. gondii HG(X)PRT that facilitates PRPP center dot Mg2+ binding by isomerization from trans to cis conformation is conserved in PfHGXPRT. Free energy calculations using the well-tempered metadynamics technique show the ligand- free enzyme to be more stable when this dipeptide is in the trans conformation than in the cis conformation. The high rotational energy barrier observed for the conformational change from experimental and computational studies permits delineation of the activation mechanism.en_US
dc.description.uri1742-2051en_US
dc.description.urihttp://dx.doi.org/10.1039/c5mb00136fen_US
dc.language.isoEnglishen_US
dc.publisherRoyal Society of Chemistryen_US
dc.rights?Royal Society of Chemistry, 2015en_US
dc.subjectBiochemistry & Molecular Biologyen_US
dc.subjectSteady-State Kineticsen_US
dc.subject2.0 Angstrom Structureen_US
dc.subjectCrystal-Structureen_US
dc.subjectEscherichia-Colien_US
dc.subjectTritrichomonas-Fetusen_US
dc.subjectMolecular-Dynamicsen_US
dc.subjectTrypanosoma-Cruzien_US
dc.subjectternary Complexen_US
dc.subjectFlexible Loopen_US
dc.subject6-Oxopurine Phosphoribosyltransferasesen_US
dc.titleSlow ligand-induced conformational switch increases the catalytic rate in Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferaseen_US
dc.typeArticleen_US
Appears in Collections:Research Articles (Balasubramanian Sundaram)

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