scholarly journals Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine

2014 ◽  
Vol 57 (22) ◽  
pp. 9693-9699 ◽  
Author(s):  
Emmanuel W. Smith ◽  
Yan Liu ◽  
Anthony E. Getschman ◽  
Francis C. Peterson ◽  
Joshua J. Ziarek ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Small Molecule ◽  
Small Molecule Ligand

scholarly journals Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate

2015 ◽  
Vol 71 (2) ◽  
pp. 199-205 ◽  
Author(s):  
George T. Lountos ◽  
Scott Cherry ◽  
Joseph E. Tropea ◽  
David S. Waugh
Keyword(s):  
Crystal Structure ◽  
Structural Analysis ◽  
Phosphatase Activity ◽  
Small Molecule ◽  
Molecular Basis ◽  
Protein Tyrosine Phosphatases ◽  
Simple Method ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Nitrophenyl Phosphate

4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.

On the propagation of errors

2013 ◽  
Vol 69 (10) ◽  
pp. 1865-1866 ◽  
Author(s):  
Mariusz Jaskolski
Keyword(s):  
Protein Data Bank ◽  
Small Molecule ◽  
Data Bank ◽  
Propagation Of Errors ◽  
Small Molecule Ligand

The policy of the Protein Data Bank (PDB) that the first deposition of a small-molecule ligand, even with erroneous atom numbering, sets a precedent over accepted nomenclature rules is disputed. Recommendations regarding ligand molecules in the PDB are suggested.

scholarly journals Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains

ChemMedChem ◽  
2018 ◽  
Vol 13 (14) ◽  
pp. 1479-1487 ◽  
Author(s):  
Andrea Dalle Vedove ◽  
Dimitrios Spiliotopoulos ◽  
Vito G. D'Agostino ◽  
Jean-Rémy Marchand ◽  
Andrea Unzue ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Small Molecule

Validation and Development of an Escherichia coli Riboflavin Pathway Phenotypic Screen Hit as a Small-Molecule Ligand of the Flavin Mononucleotide Riboswitch

2018 ◽  
pp. 19-40
Author(s):  
Carl J. Balibar ◽  
Artjohn Villafania ◽  
Christopher M. Barbieri ◽  
Nick Murgolo ◽  
Terry Roemer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Small Molecule ◽  
Flavin Mononucleotide ◽  
Phenotypic Screen ◽  
Small Molecule Ligand

scholarly journals Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

2017 ◽  
Vol 114 (7) ◽  
pp. 1708-1713 ◽  
Author(s):  
Seungkirl Ahn ◽  
Alem W. Kahsai ◽  
Biswaranjan Pani ◽  
Qin-Ting Wang ◽  
Shuai Zhao ◽  
...  
Keyword(s):  
Binding Site ◽  
G Protein ◽  
Small Molecule ◽  
Adrenergic Receptor ◽  
Camp Production ◽  
Small Molecule Library ◽  
Small Molecule Libraries ◽  
Negative Allosteric Modulator ◽  
G Protein Coupled ◽  
Small Molecule Ligand

The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein–coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR. Binding of 15 to the receptor cooperatively enhances orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists. Studies with a specific antibody that binds to an intracellular region of the β2AR suggest that 15 binds in proximity to the G-protein binding site on the cytosolic surface of the β2AR. In cell-signaling studies, 15 inhibits cAMP production through the β2AR, but not that mediated by other Gs-coupled receptors. Compound 15 also similarly inhibits β-arrestin recruitment to the activated β2AR. This study presents an allosteric small-molecule ligand for the β2AR and introduces a broadly applicable method for screening DNA-encoded small-molecule libraries against purified GPCR targets. Importantly, such an approach could facilitate the discovery of GPCR drugs with tailored allosteric effects.

Metal ions modulate the conformation and stability of a G-quadruplex with or without a small-molecule ligand

Metallomics ◽  
2015 ◽  
Vol 7 (11) ◽  
pp. 1508-1514 ◽  
Author(s):  
Huiru Lu ◽  
Shenghui Li ◽  
Jun Chen ◽  
Jing Xia ◽  
Jinchao Zhang ◽  
...  
Keyword(s):  
Metal Ions ◽  
Small Molecule ◽  
G Quadruplex ◽  
Small Molecule Ligand

Structural analysis of PI3-kinase isoforms: Identification of residues enabling selective inhibition by small molecule ATP-competitive inhibitors

2008 ◽  
Vol 477 (2) ◽  
pp. 404-410 ◽  
Author(s):  
Marketa J. Zvelebil ◽  
Michael D. Waterfield ◽  
Stephen J. Shuttleworth
Keyword(s):  
Structural Analysis ◽  
Small Molecule ◽  
Selective Inhibition ◽  
Pi3 Kinase ◽  
Competitive Inhibitors

Chemistry on the rhomboidal Ru4 faces of the clusters RU4(CO)13(?-PR2)2: Novel small molecule, ligand, and skeletal transformations

1992 ◽  
Vol 3 (3) ◽  
pp. 313-332 ◽  
Author(s):  
John F. Corrigan ◽  
Marie Dinardo ◽  
Simon Doherty ◽  
Arthur J. Carty
Keyword(s):  
Small Molecule ◽  
Small Molecule Ligand

scholarly journals Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor–ligand complex

2014 ◽  
Vol 70 (2) ◽  
pp. 451-460 ◽  
Author(s):  
Jacob Lauwring Andersen ◽  
Tenna Juul Schrøder ◽  
Søren Christensen ◽  
Dorthe Strandbygård ◽  
Lone Tjener Pallesen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Binding Mode ◽  
Membrane Glycoprotein ◽  
Type I ◽  
Ligand Complex ◽  
Neuronal Viability ◽  
The Central Nervous System ◽  
Vacuolar Protein ◽  
Small Molecule Ligand

Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin–AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.

scholarly journals Small-molecule ligand/drug representation and validation in the Protein Data Bank

2017 ◽  
Vol 73 (a2) ◽  
pp. C45-C45
Author(s):  
Genji Kurisu ◽  
Stephen K. Burley ◽  
John L. Markley ◽  
Haruki Nakamura ◽  
Sameer Velankar
Keyword(s):  
Protein Data Bank ◽  
Small Molecule ◽  
Data Bank ◽  
Small Molecule Ligand
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