Affinity Capture of p97 with Small-Molecule Ligand Bait Reveals a 3.6 Å Double-Hexamer Cryoelectron Microscopy Structure

ACS Nano ◽  
2021 ◽  
Author(s):  
Md Rejaul Hoq ◽  
Frank S. Vago ◽  
Kunpeng Li ◽  
Marina Kovaliov ◽  
Robert J. Nicholas ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cryoelectron Microscopy ◽  
Affinity Capture ◽  
Small Molecule Ligand

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.

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 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 Affinity Capture Enrichment versus Affinity Depletion: A Comparison of Strategies for Increasing Coverage of Low-Abundant Human Plasma Proteins

2020 ◽  
Vol 21 (16) ◽  
pp. 5903
Author(s):  
Nicolai Bjødstrup Palstrøm ◽  
Lars Melholt Rasmussen ◽  
Hans Christian Beck
Keyword(s):  
Mass Spectrometry ◽  
Small Molecule ◽  
Plasma Proteins ◽  
Biomarker Discovery ◽  
Plasma Samples ◽  
Label Free ◽  
Affinity Capture ◽  
Liquid Chromatography Tandem Mass ◽  
Removal System ◽  
Equalization Method

In the present study, we evaluated four small molecule affinity-based probes based on agarose-immobilized benzamidine (ABA), O-Phospho-L-Tyrosine (pTYR), 8-Amino-hexyl-cAMP (cAMP), or 8-Amino-hexyl-ATP (ATP) for their ability to remove high-abundant proteins such as serum albumin from plasma samples thereby enabling the detection of medium-to-low abundant proteins in plasma samples by mass spectrometry-based proteomics. We compared their performance with the most commonly used immunodepletion method, the Multi Affinity Removal System Human 14 (MARS14) targeting the top 14 most abundant plasma proteins and also the ProteoMiner protein equalization method by label-free quantitative liquid chromatography tandem mass spectrometry (LC-MSMS) analysis. The affinity-based probes demonstrated a high reproducibility for low-abundant plasma proteins, down to picomol per mL levels, compared to the Multi Affinity Removal System (MARS) 14 and the Proteominer methods, and also demonstrated superior removal of the majority of the high-abundant plasma proteins. The ABA-based affinity probe and the Proteominer protein equalization method performed better compared to all other methods in terms of the number of analyzed proteins. All the tested methods were highly reproducible for both high-abundant plasma proteins and low-abundant proteins as measured by correlation analyses of six replicate experiments. In conclusion, our results demonstrated that small-molecule based affinity-based probes are excellent alternatives to the commonly used immune-depletion methods for proteomic biomarker discovery studies in plasma. Data are available via ProteomeXchange with identifier PXD020727.

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

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
Sign in / Sign up

Export Citation Format

Share Document