scholarly journals Ligand promiscuity through the eyes of the aminoglycosideN3 acetyltransferase IIa

2013 ◽  
Vol 22 (7) ◽  
pp. 916-928 ◽  
Author(s):  
Adrianne L. Norris ◽  
Engin H. Serpersu
Keyword(s):  
Ligand Promiscuity

scholarly journals Induction of ligand promiscuity of αVβ3 integrin by mechanical force

2020 ◽  
Vol 133 (9) ◽  
pp. jcs242404 ◽  
Author(s):  
Michael Bachmann ◽  
Markus Schäfer ◽  
Vasyl V. Mykuliak ◽  
Marta Ripamonti ◽  
Lia Heiser ◽  
...  
Keyword(s):  
Mechanical Force ◽  
Αvβ3 Integrin ◽  
Ligand Promiscuity

Ligand promiscuity within the internal cavity of Epiphyas postvittana Takeout 1 protein

2013 ◽  
Vol 182 (3) ◽  
pp. 259-263 ◽  
Author(s):  
Cyril Hamiaux ◽  
Lisa Basten ◽  
David R. Greenwood ◽  
Edward N. Baker ◽  
Richard D. Newcomb
Keyword(s):  
Internal Cavity ◽  
Epiphyas Postvittana ◽  
Ligand Promiscuity

scholarly journals Biosynthesis of a Novel Glutamate Racemase Containing a Site-Specific 7-Hydroxycoumarin Amino Acid: Enzyme–Ligand Promiscuity Revealed at the Atomistic Level

2015 ◽  
Vol 1 (7) ◽  
pp. 364-373 ◽  
Author(s):  
Sondra F. Dean ◽  
Katie L. Whalen ◽  
M. Ashley Spies
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Glutamate Racemase ◽  
A Site ◽  
Ligand Promiscuity

scholarly journals Structural determinants driving homoserine lactone ligand selection in thePseudomonas aeruginosaLasR quorum-sensing receptor

2018 ◽  
Vol 116 (1) ◽  
pp. 245-254 ◽  
Author(s):  
Amelia R. McCready ◽  
Jon E. Paczkowski ◽  
Brad R. Henke ◽  
Bonnie L. Bassler
Keyword(s):  
Quorum Sensing ◽  
Ligand Binding ◽  
Homoserine Lactone ◽  
Communication Process ◽  
Signal Molecules ◽  
Structural Determinants ◽  
Homoserine Lactones ◽  
Ligand Selectivity ◽  
Ligand Promiscuity

Quorum sensing is a cell–cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use thePseudomonas aeruginosaLasR quorum-sensing receptor to explore signal discrimination. The cognate autoinducer, 3OC12homoserine lactone (3OC12HSL), is a more potent activator of LasR than other homoserine lactones. However, other homoserine lactones can elicit LasR-dependent quorum-sensing responses, showing that LasR displays ligand promiscuity. We identify mutants that alter which homoserine lactones LasR detects. Substitution at residue S129 decreases the LasR response to 3OC12HSL, while enhancing discrimination against noncognate autoinducers. Conversely, the LasR L130F mutation increases the potency of 3OC12HSL and other homoserine lactones. We solve crystal structures of LasR ligand-binding domains complexed with noncognate autoinducers. Comparison with existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop near the ligand-binding site. We show that LasR variants with modified ligand preferences exhibit altered quorum-sensing responses to autoinducers in vivo. We suggest that possessing some ligand promiscuity endows LasR with the ability to optimally regulate quorum-sensing traits.

Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D3 Receptor (D3R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)

2019 ◽  
Vol 62 (10) ◽  
pp. 5132-5147 ◽  
Author(s):  
Sean W. Reilly ◽  
Aladdin A. Riad ◽  
Chia-Ju Hsieh ◽  
Kristoffer Sahlholm ◽  
Daniel A. Jacome ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Dopamine D3 ◽  
G Protein Coupled ◽  
Ligand Promiscuity

scholarly journals Pyranose Dehydrogenase Ligand Promiscuity: A Generalized Approach to Simulate Monosaccharide Solvation, Binding, and Product Formation

2014 ◽  
Vol 10 (12) ◽  
pp. e1003995 ◽  
Author(s):  
Michael M. H. Graf ◽  
Lin Zhixiong ◽  
Urban Bren ◽  
Dietmar Haltrich ◽  
Wilfred F. van Gunsteren ◽  
...  
Keyword(s):  
Product Formation ◽  
Pyranose Dehydrogenase ◽  
Ligand Promiscuity

scholarly journals Ligand binding promiscuity of αVβ3 integrin is enlarged in response to mechanical force

2017 ◽  
Author(s):  
Michael Bachmann ◽  
Markus Schäfer ◽  
Vasyl V. Mykuliak ◽  
Marta Ripamonti ◽  
Lia Heiser ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Mechanical Load ◽  
Matrix Proteins ◽  
Αvβ3 Integrin ◽  
Superresolution Imaging ◽  
Hybrid Domain ◽  
Open Conformation ◽  
Dynamics Simulations ◽  
Integrin Ligand ◽  
Ligand Promiscuity

AbstractαVβ3 integrin recognizes multiple extracellular matrix proteins, including vitronectin (Vn) and fibronectin (Fn). However, cell experiments are frequently performed on homogenously coated substrates with only one integrin ligand present. Here, we employed binary-choice substrates of Fn and Vn to dissect αVβ3 integrin-mediated binding to both ligands on the subcellular scale. Superresolution imaging revealed that αVβ3 integrin preferred binding to Vn under various conditions. In contrast, binding to Fn required mechanical load on αVβ3 integrin. Integrin mutations, structural analysis, and molecular dynamics simulations established a model where the extended-closed conformation of αVβ3 integrin binds Vn but not Fn. Force-mediated hybrid domain swing-out characterizes the extended-open conformation needed for efficient Fn binding. Thus, force-dependent conformational changes in αVβ3 integrin increase the number of available ligands and therefore the ligand promiscuity of this integrin. These findings for αVβ3 integrin were shown to regulate cell migration and mechanotransduction differentially on Fn compared to Vn and therefore to regulate cell behavior.

scholarly journals A multi-label approach to target prediction taking ligand promiscuity into account

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Avid M Afzal ◽  
Hamse Y Mussa ◽  
Richard E Turner ◽  
Andreas Bender ◽  
Robert C Glen
Keyword(s):  
Target Prediction ◽  
Ligand Promiscuity
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