<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gharui, Sowmomita</style></author><author><style face="normal" font="default" size="100%">Sengupta, Durba</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Characterization of the conformational hotspots of the RNA-dependent RNA polymerase complex identifies a unique structural malleability of nsp8</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Physical Chemistry B</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">128</style></volume><pages><style face="normal" font="default" size="100%">9959-9975</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Several antiviral therapeutic approaches have been targeted toward the RNA-dependent RNA polymerase (RdRp) complex that is involved in viral genome replication. In SARS-CoV-2, although the RdRp is a multiprotein complex, the focus has been on the ligand binding catalytic core (nonstructural protein nsp12), and not the multiprotein functional dynamics. In this study, we focus on the conformational ensembles of the RdRp complex and their modulation by the presence of RNA, performing comprehensive microsecond-scale atomistic simulations of the apo- and RNA-bound complex. We delineate the differential impact of RNA on the constituent proteins, such as conformational polymorphisms, dominant segment-specific fluctuations, and the switch in dynamical crosstalk within the complex. We distinguish dynamical signatures of nsp7, nsp8, and nsp12 in the apo-state that are reduced in the presence of the RNA and appear to ``prime'' the complex for activity. Importantly, we identify a unique structural malleability of the nsp8 protein with high conformational heterogeneity in the apo state, especially at three sites (Y71 for nsp8A, and D52 and A66 for nsp8B). Our work highlights the functional implications of the polymorphism of nsp8 structures and reveals possibilities for the development of allosteric inhibitors.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">41</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
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	3.3&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sheikh, Amreen B.</style></author><author><style face="normal" font="default" size="100%">Jathar, Swaraj M.</style></author><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author><author><style face="normal" font="default" size="100%">Kulkarni, Mahesh J.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Characterization of S-homocysteinylation of Human Insulin and Its Implications in Diabetes</style></title><secondary-title><style face="normal" font="default" size="100%">Protein Journal</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Disulfide bonds</style></keyword><keyword><style  face="normal" font="default" size="100%">Homocysteinylation</style></keyword><keyword><style  face="normal" font="default" size="100%">insulin</style></keyword><keyword><style  face="normal" font="default" size="100%">Mass spectrometry</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">44</style></volume><pages><style face="normal" font="default" size="100%">598-610</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Homocysteine thiolactone is a reactive thiol known for its interaction with various proteins. Nevertheless, there exists a paucity of information concerning the interaction between homocysteine thiolactone and human insulin, particularly regarding the mechanism by which homocysteine facilitates the reduction of disulfide bonds within insulin. In the present study, we have elucidated the binding sites of homocysteine to the cysteine residues (A6-B7 and A20-B19) that are implicated in the formation of intermolecular disulfide bonds in insulin through an in vitro reaction analyzed via LC-ESI MS/MS. This results in a reduction of disulfide bonds linking the A and B chains, which was corroborated by MALDI-TOF-MS and ESI-MS analysis. The secondary structure of insulin is affected by this modification, as evidenced by circular dichroism spectroscopy. In-silico studies also show that homocysteine affects the insulin structure. A glucose uptake assay conducted in Chinese hamster ovary (CHO) cells that stably express the insulin receptor revealed that HC-modified insulin is less effective in inducing glucose uptake compared to native insulin, suggesting that HC-induced structural modifications in insulin influence functional activity. This study provides insight into the HC-induced structural and functional changes in insulin and discusses the consequent implications for diabetes.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
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	2.3&lt;/p&gt;
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