scholarly journals Site-Resolved and Quantitative Characterization of Very Weak Protein–Ligand Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 1398-1402 ◽  
Author(s):  
Brian Fuglestad ◽  
Nicole E. Kerstetter ◽  
A. Joshua Wand
Keyword(s):  
Quantitative Characterization ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

scholarly journals Characterization of protein-ligand binding interactions of enoyl-ACP reductase (FabI) by native MS reveals allosteric effects of coenzymes and the inhibitor triclosan

2019 ◽  
Author(s):  
P. Matthew Joyner ◽  
Denise P. Tran ◽  
Muhammad A. Zenaidee ◽  
Joseph A. Loo
Keyword(s):  
Fatty Acid Synthase ◽  
Antibacterial Drug ◽  
Allosteric Effect ◽  
The Past ◽  
Protein Ligand Interactions ◽  
Native Ms ◽  
Ligand Interactions ◽  
Enoyl Acp Reductase ◽  
The Subject

AbstractThe enzyme enoyl-ACP reductase (also called FabI in bacteria) is an essential member of the fatty acid synthase II pathway in plants and bacteria. This enzyme is the target of the antibacterial drug triclosan and has been the subject of extensive studies for the past 20 years. Despite the large number of reports describing the biochemistry of this enzyme, there have been no studies that provided direct observation of the protein and its various ligands. Here we describe the use of native MS to characterize the protein-ligand interactions of FabI with its coenzymes NAD+ and NADH and with the inhibitor triclosan. Measurements of the gas-phase affinities of the enzyme for these ligands yielded values that are in close agreement with solution-phase affinity measurements. Additionally, FabI is a homotetramer and we were able to measure the affinity of each subunit for each coenzyme, which revealed that both coenzymes exhibit a positive homotropic allosteric effect. An allosteric effect was also observed in association with the inhibitor triclosan. These observations provide new insights into this well-studied enzyme and suggest that there may still be gaps in the existing mechanistic models that explain FabI inhibition.

NMR investigation of protein–ligand interactions for G-protein coupled receptors

2019 ◽  
Vol 11 (14) ◽  
pp. 1811-1825 ◽  
Author(s):  
Claire Raingeval ◽  
Isabelle Krimm
Keyword(s):  
Conformational Changes ◽  
Functional Characterization ◽  
Allosteric Modulation ◽  
G Protein Coupled Receptors ◽  
Nmr Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Therapeutic Compounds ◽  
G Protein Coupled

In this review, we report NMR studies of ligand–GPCR interactions, including both ligand-observed and protein-observed NMR experiments. Published studies exemplify how NMR can be used as a powerful tool to design novel GPCR ligands and investigate the ligand-induced conformational changes of GPCRs. The strength of NMR also lies in its capability to explore the diverse signaling pathways and probe the allosteric modulation of these highly dynamic receptors. By offering unique opportunities for the identification, structural and functional characterization of GPCR ligands, NMR will likely play a major role for the generation of novel molecules both as new tools for the understanding of the GPCR function and as therapeutic compounds for a large diversity of pathologies.

Nuclear Magnetic Resonance of Hyperpolarized Fluorine for Characterization of Protein–Ligand Interactions

2012 ◽  
Vol 134 (42) ◽  
pp. 17448-17451 ◽  
Author(s):  
Youngbok Lee ◽  
Haifeng Zeng ◽  
Simon Ruedisser ◽  
Alvar D. Gossert ◽  
Christian Hilty
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Nuclear Magnetic

scholarly journals Characterization of protein–ligand interactions by SABRE

2021 ◽  
Author(s):  
Ratnamala Mandal ◽  
Pierce Pham ◽  
Christian Hilty
Keyword(s):  
Ligand Binding ◽  
Polarization Transfer ◽  
Binding Interactions ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

Protein–ligand binding interactions are characterized by the para-H2 based hyperpolarization technique SABRE and flow-NMR. Binding to the protein is identified by R2 change of a ligand first interacting with the Ir polarization transfer catalyst.

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