Molecular details of ligand selectivity determinants in a promiscuous β-glucan periplasmic binding protein

dc.contributorMiddle Tennessee State University. Department of Chemistryen_US
dc.contributor.authorMunshi, Parthapratimen_US
dc.contributor.authorStanley, Christopher Ben_US
dc.contributor.authorGhimire-Rijal, Sudipaen_US
dc.contributor.authorLu, Xunen_US
dc.contributor.authorMyles, Dean Aen_US
dc.contributor.authorCuneo, Matthew Jen_US
dc.date.accessioned2014-06-24T15:34:42Z
dc.date.available2014-06-24T15:34:42Z
dc.date.issued2013-09-27en_US
dc.description.abstractBackground Members of the periplasmic binding protein (PBP) superfamily utilize a highly conserved inter-domain ligand binding site that adapts to specifically bind a chemically diverse range of ligands. This paradigm of PBP ligand binding specificity was recently altered when the structure of the Thermotoga maritima cellobiose-binding protein (tmCBP) was solved. The tmCBP binding site is bipartite, comprising a canonical solvent-excluded region (subsite one), adjacent to a solvent-filled cavity (subsite two) where specific and semi-specific ligand recognition occur, respectively.en_US
dc.description.abstractResults A molecular level understanding of binding pocket adaptation mechanisms that simultaneously allow both ligand specificity at subsite one and promiscuity at subsite two has potentially important implications in ligand binding and drug design studies. We sought to investigate the determinants of ligand binding selectivity in tmCBP through biophysical characterization of tmCBP in the presence of varying ßglucan oligosaccharides. Crystal structures show that whilst the amino acids that comprise both the tmCBP subsite one and subsite two binding sites remain fixed in conformation regardless of which ligands are present, the rich hydrogen bonding potential of water molecules may facilitate the ordering and the plasticity of this unique PBP binding site.en_US
dc.description.abstractConclusions The identification of the roles these water molecules play in ligand recognition suggests potential mechanisms that can be utilized to adapt a single ligand binding site to recognize multiple distinct ligands.en_US
dc.identifier.citationBMC Structural Biology. 2013 Sep 27;13:18en_US
dc.identifier.urihttp://jewlscholar.mtsu.edu/handle/mtsu/4237
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.subjectPeriplasmic binding proteinen_US
dc.subjectCarbohydrate recognitionen_US
dc.subjectLaminarinen_US
dc.subjectABC transporten_US
dc.subjectLigand specificityen_US
dc.titleMolecular details of ligand selectivity determinants in a promiscuous β-glucan periplasmic binding proteinen_US
dc.typeResearch Articleen_US

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