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dc.contributor.authorKarthigeyan, Dhanasekaran
dc.contributor.authorSiddhanta, Soumik
dc.contributor.authorKishore, Annavarapu Hari
dc.contributor.authorPerumal, Sathya S. R. R.
dc.contributor.authorAgren, Hans
dc.contributor.authorSudevan, Surabhi
dc.contributor.authorBhat, Akshay V.
dc.contributor.authorBalasubramanyam, Karanam
dc.contributor.authorSubbegowda, Rangappa Kanchugarakoppal
dc.contributor.authorKundu, Tapas Kumar
dc.contributor.authorNarayana, Chandrabhas
dc.identifier.citationKarthigeyan, D; Siddhanta, S; Kishore, AH; Perumal, SSRR; Agren, H; Sudevan, S; Bhat, AV; Balasubramanyam, K; Subbegowda, RK; Kundu, TK; Narayana, C, SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery tool. Proceedings of The National Academy of Sciences of The United States of America 2014, 111 (29) 10416-10421,
dc.identifier.citationProceedings of The National Academy of Sciences of The United States of Americaen_US
dc.descriptionRestricted Accessen_US
dc.description.abstractWe demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr-212 residue to specifically inhibit its activity. Based on SERS studies, molecular docking, molecular dynamics simulation, biochemical assays, and point mutation-based validation, we demonstrate the surface-binding mode of this molecule in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A versus human Aurora B kinase in vivo. The application of SERS to identify the specific interactions between small molecules and therapeutically important proteins by differentiating competitive and noncompetitive inhibition demonstrates its ability as a complementary technique. We also present felodipine as a specific inhibitor for oncogenic Aurora A kinase. Felodipine retards the rate of tumor progression in a xenografted nude mice model. This study reveals a potential surface pocket that may be useful for developing small molecules by selectively targeting the Aurora family kinases.en_US
dc.publisherNational Academy of Sciencesen_US
dc.rights@National Academy of Sciences, 2014en_US
dc.subjectVibrational Spectroscopyen_US
dc.subjectStructure-Activity Relationshipen_US
dc.subjectLigand Bindingen_US
dc.subjectSurface-Enhanced Ramanen_US
dc.subjectSmall-Molecule Inhibitoren_US
dc.subjectProtein-Ligand Interactionsen_US
dc.subjectAurora-A Kinaseen_US
dc.subjectHistone Acetyltransferaseen_US
dc.titleSERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery toolen_US
Appears in Collections:Research Articles (Chandrabhas N.)
Research Papers (Tapas K. Kundu)

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