Molecular details of ligand selectivity determinants in a promiscuous β-glucan periplasmic binding protein
Parthapratim Munshi,Parthapratim Munshi,Parthapratim Munshi,Christopher B. Stanley,Sudipa Ghimire-Rijal,Xun Lu,Dean A. A. Myles,Matthew J. Cuneo +7 more
TLDR
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 in the presence of varying β-glucan oligosaccharides.Abstract:
Background: 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. Results: 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 β-glucan 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. Conclusions: 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.read more
Citations
More filters
Journal ArticleDOI
Cooperative Electrostatic Interactions Drive Functional Evolution in the Alkaline Phosphatase Superfamily.
Alexandre Barrozo,Fernanda Duarte,Paul Bauer,Alexandra T. P. Carvalho,Shina Caroline Lynn Kamerlin +4 more
TL;DR: This work model the selectivity of two multiply promiscuous members of the alkaline phosphatase superfamily, namely the phosphonate monoester hydrolases from Burkholderia caryophylli and Rhizobium leguminosarum and suggest that this phenomenon is a generalized feature driving selectivity and promiscuity within this superfamily and can be in turn used for artificial enzyme design.
Journal ArticleDOI
Periplasmic solute-binding proteins: Structure classification and chitooligosaccharide recognition
TL;DR: The overall structural feature of the Vibrios CBPs is most similar to the cellobiose-binding orthologue from the hyperthermophilic bacterium Thermotoga maritima, which provides an opportunity to engineer the substrate specificity of the proteins and to control the uptake of chitinous and cellulosic nutrients in marine bacteria.
Journal ArticleDOI
Differential Substrate Recognition by Maltose Binding Proteins Influenced by Structure and Dynamics.
Shantanu Shukla,Shantanu Shukla,Khushboo Bafna,Caeley Gullett,Dean A. A. Myles,Dean A. A. Myles,Pratul K. Agarwal,Matthew J. Cuneo,Matthew J. Cuneo +8 more
TL;DR: Comparing quantitative protein-substrate interactions and dynamical properties of tmMBPs with those of the promiscuous ecMBP and disaccharide selective Thermococcus litoralis MBP provides insights into the features that enable selective binding.
Journal ArticleDOI
Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding
Le Li,Sudipa Ghimire-Rijal,Sarah L Lucas,Christopher B. Stanley,Edward Wright,Pratul K. Agarwal,Dean A. A. Myles,Matthew J. Cuneo +7 more
TL;DR: This work identifies an additional state of the PBP that is also allosterically regulated by the ligand, and minimizes futile ATP hydrolysis in the transporter, a phenomenon in which ATP Hydrolysis is not coupled to metabolite transport.
Journal ArticleDOI
Conformational Trapping of a β-Glucosides-Binding Protein Unveils the Selective Two-Step Ligand-Binding Mechanism of ABC Importers.
TL;DR: This study reports, for the first time, four different structural states of the protein βGlyBP, revealing its conformational changes upon ligand binding and suggesting a two-step induced-fit mechanism.
References
More filters
Journal ArticleDOI
The Protein Data Bank
Helen M. Berman,John D. Westbrook,Zukang Feng,Gary L. Gilliland,Talapady N. Bhat,Helge Weissig,Ilya N. Shindyalov,Philip E. Bourne +7 more
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Book ChapterDOI
Processing of X-ray diffraction data collected in oscillation mode
Zbyszek Otwinowski,Wladek Minor +1 more
TL;DR: The methods presented in the chapter have been applied to solve a large variety of problems, from inorganic molecules with 5 A unit cell to rotavirus of 700 A diameters crystallized in 700 × 1000 × 1400 A cell.
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI
The CCP4 suite: programs for protein crystallography
TL;DR: The CCP4 (Collaborative Computational Project, number 4) program suite is a collection of programs and associated data and subroutine libraries which can be used for macromolecular structure determination by X-ray crystallography.