02449nas a2200265   4500008004100000022001400041245010100055210006900156260000800225300001000233490000700243520157500250653001701825653001201842653001901854653001901873653003301892653002401925100001701949700002001966700002601986700002002012700002102032856013002053       2016                        eng d  a0141-813000aStructural-functional insights and studies on saccharide binding of Sophora japonica seed lectin0 aStructuralfunctional insights and studies on saccharide binding   cOCT  a75-840 v913 a<p>Functional and conformational transitions of the Sophora japonica seed lectin (SJL) were studied in detail using bioinformatics and biophysical tools. Homology model of the lectin displayed all the characteristics of the legume lectin monomer and the experimental observations correlated well with the structural information. In silico studies were performed by protein-ligand docking, calculating the respective binding energies and the residues involved in the interactions were derived from LigPlot(+) analysis. Fluorescence titrations showed three times higher affinity of T-antigen disaccharide than N-acetyl galactosamine (GaINAc) towards SJL indicating extended sugar binding site of the lectin. Thermodynamic parameters of T-antigen binding to SJL indicated the process to be endothermic and entropically driven while those of GaINAc showed biphasic process. SDS-PAGE showed post-translationally modified homotetrameric species of the lectin under native conditions. In presence of guanidine hydrochloride (0.5-5.0 M), the tetramer first dissociated into dimers followed by unfolding of the protein as indicated by size exclusion chromatography, fluorescence and CD spectroscopy. Different structural rearrangements were observed during thermal denaturation of SJL at physiological pH 7.2, native pH 8.5 and molten globule inducing pH 1.0. Topological information revealed by solute quenching studies at respective pH indicated differential hydrophobic environment and charge density around tryptophan residues. (C) 2016 Elsevier B.V. All rights reserved.</p>10aDissociation10adocking10aHomology model10aLigand binding10aSophora japonica seed lectin10aThermal transitions1 aYadav, Priya1 aShahane, Ganesh1 aRamasamy, Sureshkumar1 aSengupta, Durba1 aGaikwad, Sushama  uhttps://library.ncl.res.in/content/structural-functional-insights-and-studies-saccharide-binding-sophora-japonica-seed-lectin02473nas a2200253   4500008004100000022001400041245010500055210006900160260000900229300001200238490000800250520154700258653003701805653004501842653003101887653001901918653003601937653003001973100002202003700002202025700002202047700002002069856013002089       2022                        eng d  a0141-813000aAllosteric modulation of the chemokine receptor-chemokine CXCR4-CXCL12 complex by tyrosine sulfation0 aAllosteric modulation of the chemokine receptorchemokine CXCR4CX  cMAY   a812-8220 v2063 a<p>
	The chemokine receptor CXCR4 and its cognate ligand CXCL12 mediate pathways that lead to cell migration and chemotaxis. Although the structural details of related receptor-ligand complexes have been resolved, the roles of the N-terminal domain of the receptor and post-translational sulfation that are determinants of ligand selectivity and affinity remain unclear. Here, we analyze the structural dynamics induced by receptor sulfation by combining molecular dynamics, docking and network analysis. The sulfotyrosine residues, 7YsN-term, 12Ys(N-term) and 21Ys(N-term) allow the N-terminal domain of the apo-sulfated receptor to adopt an ``open `` conformation that appears to facilitate ligand binding. The overall topology of the CXCR4-CXCL12 complex is independent of the sulfation state, but an extensive network of protein-protein interactions characterizes the sulfated receptor, in line with its increased ligand affinity. The altered interactions of sulfotyrosine residues, such as 21Ys(N-term)- 47R(CXCL12) replacing the 21Y(N-term)-13F(CXCL12) interaction, propagate via allosteric pathways towards the receptor lumen. In particular, our results suggest that the experimentally-reported receptor-ligand interactions 262D(6.58)- 8R(CXCL12) and 277E(7.28)-12R(CXCL12) could be dependent on the sulfation state of the receptor and need to be carefully analyzed. Our work is an important step in understanding chemokine-receptor interactions and how post-translational modifications could modulate receptor-ligand complexes.</p>
10aAllosteric communication pathway10aAtomistic molecular dynamics simulations10aG protein-coupled receptor10aLigand binding10aPost-translational modification10aProtein-protein interface1 aSonawani, Archana1 aKharche, Shalmali1 aDasgupta, Debjani1 aSengupta, Durba  uhttps://library.ncl.res.in/content/allosteric-modulation-chemokine-receptor-chemokine-cxcr4-cxcl12-complex-tyrosine-sulfation