scholarly journals Characterizing the Fatty Acid Binding Site in the Cavity of Potassium Channel KcsA

Biochemistry ◽  
2012 ◽  
Vol 51 (40) ◽  
pp. 7996-8002 ◽  
Author(s):  
Natalie Smithers ◽  
Juan H. Bolivar ◽  
Anthony G. Lee ◽  
J. Malcolm East
Keyword(s):  
Fatty Acid ◽  
Potassium Channel ◽  
Binding Site ◽  
Fatty Acid Binding ◽  
Potassium Channel Kcsa ◽  
Fatty Acid Binding Site

Identification of the fatty acid binding site on glutathione S-transferase P

1992 ◽  
Vol 189 (1) ◽  
pp. 197-205 ◽  
Author(s):  
Jun Nishihira ◽  
Teruo Ishibashi ◽  
Masaharu Sakai ◽  
Shinzo Nishi ◽  
Hidemasa Kondo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Glutathione S Transferase ◽  
Fatty Acid Binding ◽  
Fatty Acid Binding Site

scholarly journals Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands binding the Free Fatty Acid Pocket of SARS-CoV-2 Spike Protein

2020 ◽  
Author(s):  
Deborah Shoemark ◽  
Charlotte Colenso ◽  
Christine Toelzer ◽  
Kapil Gupta ◽  
Richard Sessions ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Spike Protein ◽  
Fatty Acid Binding ◽  
Open Conformation ◽  
Interaction Interface ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Fatty Acid Binding Site

<p>Following our recent identification of a fatty acid binding site in the SARS-CoV-2 spike protein (Toelzer <i>et al., Science</i> eabd3255 (2020)), we investigate the binding of linoleate and other potential ligands at this site using molecular dynamics simulations. The results support the hypothesis that linoleate stabilises the locked form of the spike, in which its interaction interface for the ACE2 receptor is occluded. The simulations indicate weaker binding of linoleate to the partially open conformation. Simulations of dexamethasone bound at this site indicate that it binds similarly to linoleate, and thus may also stabilize a locked spike conformation. In contrast, simulations suggest that cholesterol bound at this site may destabilize the locked conformation, and in the open conformation, may preferentially bind at an alternative site in the hinge region between the receptor binding domain and the domain below, which could have functional relevance. We also use molecular docking to identify potential ligands that may bind at the fatty acid binding site, using the Bristol University Docking Engine (BUDE). BUDE docking successfully reproduces the linoleate complex and also supports binding of dexamethasone at the spike fatty acid site. Virtual screening of a library of approved drugs identifies vitamins D, K and A, as well as retinoid ligands with experimentally demonstrated activity against SARS-CoV-2 replication <i>in vitro</i>, as also potentially able to bind at this site. Our data suggest that the fatty acid binding site of the SARS-CoV-2 spike protein may bind a diverse array of candidate ligands. Targeting this site with small molecules, including dietary components such as vitamins, which may stabilise its locked conformation and represents a potential avenue for novel therapeutics or prophylaxis for COVID-19.</p>

scholarly journals The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour

2021 ◽  
Author(s):  
Ana Sofia Oliveira ◽  
Deborah Shoemark ◽  
Amaurys Avila Ibarra ◽  
Andrew D. Davidson ◽  
Imre Berger ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Acid Site ◽  
Host Cells ◽  
Spike Protein ◽  
Nonequilibrium Molecular Dynamics ◽  
Binding Motif ◽  
Fatty Acid Binding ◽  
Furin Cleavage Site ◽  
Fatty Acid Binding Site

The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. The results also show significant differences in behaviour between clinical variants of the spike: e.g. the D614G mutation shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication.

Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin

2017 ◽  
Vol 130 (4) ◽  
pp. 1056-1060 ◽  
Author(s):  
Lea Wenskowsky ◽  
Herman Schreuder ◽  
Volker Derdau ◽  
Hans Matter ◽  
Julia Volkmar ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
Fatty Acid Binding ◽  
High Affinity ◽  
Identification And Characterization ◽  
Fatty Acid Binding Site
Sign in / Sign up

Export Citation Format

Share Document