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Papers by Mayank Boob
The Journal of Physical Chemistry B
Cyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK... more Cyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK activity on Cyclin levels is established, molecular mechanisms that regulate their binding are less studied. Here, we show that CDKl:Cyclin-B interactions are regulated by acetylation, which was hitherto unknown. We demonstrate that cell cycle dependent acetylation of the evolutionarily conserved catalytic lysine in CDK1 or eliminating its charge state abrogates Cyclin-B binding. Opposing activities of SIRT1 and P300 regulate acetylation, which marks a reserved pool of CDK1. Our high resolution structural analyses into the formation of kinase competent CDK1: Cyclin-B complex have unveiled long-range effects of catalytic lysine in configuring the CDK1 interface for Cyclin-B binding. Cells expressing acetylation mimic mutant of Cdc2 in yeast are arrested in G2 and fail to divide. Thus, by illustrating cell cycle dependent deacetylation as a determinant of CDK1:Cyclin-B interaction, our re...
Biophysical Journal
Previous work with the four-helix bundle protein cytochrome c' from Rhodopseudomonas palustris us... more Previous work with the four-helix bundle protein cytochrome c' from Rhodopseudomonas palustris using histidine-heme loop formation thermodynamic methods revealed fold-specific deviations from random coil behavior in its denatured state ensemble. To examine the generality of this finding, we extend this work to a three-helix bundle polypeptide, the second ubiquitin
Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability ... more Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability under stress. The natural osmolyte trimethylamine N-oxide (TMAO) is used by marine animals to counteract the effect of pressure denaturation at large depths. The molecular mechanism of TMAO stabilization against pressure and urea denaturation has been extensively studied, but the effect of TMAO against high temperature has not been addressed. To delineate the effect of TMAO on folded and unfolded ensembles at different temperatures, we study a mutant of the well-characterized, fastfolding model protein B (PRB). We have carried out extensive, >190 µs in total, all-atom simulations of thermal folding/unfolding of PRB at multiple temperatures and concentrations of TMAO. The simulations captured folding and unfolding events and show an increased stability of PRB in presence of TMAO. At higher TMAO concentration, intermediate ensembles are gradually more favored over the unfolded state. Qu...
The Journal of Physical Chemistry B
Cyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK... more Cyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK activity on Cyclin levels is established, molecular mechanisms that regulate their binding are less studied. Here, we show that CDKl:Cyclin-B interactions are regulated by acetylation, which was hitherto unknown. We demonstrate that cell cycle dependent acetylation of the evolutionarily conserved catalytic lysine in CDK1 or eliminating its charge state abrogates Cyclin-B binding. Opposing activities of SIRT1 and P300 regulate acetylation, which marks a reserved pool of CDK1. Our high resolution structural analyses into the formation of kinase competent CDK1: Cyclin-B complex have unveiled long-range effects of catalytic lysine in configuring the CDK1 interface for Cyclin-B binding. Cells expressing acetylation mimic mutant of Cdc2 in yeast are arrested in G2 and fail to divide. Thus, by illustrating cell cycle dependent deacetylation as a determinant of CDK1:Cyclin-B interaction, our re...
Biophysical Journal
Previous work with the four-helix bundle protein cytochrome c' from Rhodopseudomonas palustris us... more Previous work with the four-helix bundle protein cytochrome c' from Rhodopseudomonas palustris using histidine-heme loop formation thermodynamic methods revealed fold-specific deviations from random coil behavior in its denatured state ensemble. To examine the generality of this finding, we extend this work to a three-helix bundle polypeptide, the second ubiquitin
Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability ... more Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability under stress. The natural osmolyte trimethylamine N-oxide (TMAO) is used by marine animals to counteract the effect of pressure denaturation at large depths. The molecular mechanism of TMAO stabilization against pressure and urea denaturation has been extensively studied, but the effect of TMAO against high temperature has not been addressed. To delineate the effect of TMAO on folded and unfolded ensembles at different temperatures, we study a mutant of the well-characterized, fastfolding model protein B (PRB). We have carried out extensive, >190 µs in total, all-atom simulations of thermal folding/unfolding of PRB at multiple temperatures and concentrations of TMAO. The simulations captured folding and unfolding events and show an increased stability of PRB in presence of TMAO. At higher TMAO concentration, intermediate ensembles are gradually more favored over the unfolded state. Qu...