Topic
Linoleic acid binding
About: Linoleic acid binding is a research topic. Over the lifetime, 10 publications have been published within this topic receiving 299 citations.
Papers
TL;DR: Soybean lipoxygenase isoenzyme L3 represents a second example (after L1) of the X-ray structure (R = 17% at 2.6 A resolution) for a member of the large family of Lipoxygenases as mentioned in this paper.
Abstract: Soybean lipoxygenase isoenzyme L3 represents a second example (after L1) of the X-ray structure (R = 17% at 2.6 A resolution) for a member of the large family of lipoxygenases. L1 and L3 have different characteristics in catalysis, although they share 72% sequence identity (the changes impact 255 amino acids) and similar folding (average C alpha rms deviation of 1 A). The critical nonheme iron site has the same features as for L1:3O and 3N in pseudo C3v orientation, with two oxygen atoms (from Asn713 and water) at a nonbinding distance. Asn713 and His518 are strategically located at the junction of three cavities connecting the iron site with the molecule surface. The most visible differences between L1 and L3 isoenzymes occur in and near these cavities, affecting their accessibility and volume. Among the L1/L3 substitutions Glu256/ Thr274, Tyr409/His429, and Ser747/Asp766 affect the salt bridges (L1: Glu256...His248 and Asp490...Arg707) that in L1 restrict the access to the iron site from two opposite directions. The L3 molecule has a passage going through the whole length of the helical domain, starting at the interface with the Nt-domain (near 25-27 and 254-278) and going to the opposite end of the Ct-domain (near 367, 749). The substrate binding and the role of His513, His266, His776 (and other residues nearby) are illustrated and discussed by using models of linoleic acid binding. These hypotheses provide a possible explanation for a stringent stereo-specificity of catalytic products in L1 (that produces predominantly 13-hydroperoxide) versus the lack of such specificity in L3 (that turns out a mixture of 9- and 13-hydroperoxides and their diastereoisomers).
158 citations
TL;DR: Binding experiments with linoleic acid (LA) as polyunsaturated fatty acid (PUFA) model showed that LA would bind to OVAn by mean of hydrophobic interactions, suggesting that buried hydrophilic residues were exposed to the aqueous medium.
84 citations
TL;DR: It was concluded that limited enzymatic hydrolysis could deteriorate the specific site on BLG structure necessary for binding LA and produce a decrease in BLG ability for bindingLA.
51 citations
TL;DR: In this article, the authors used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the receptor-binding domain (RBD) that have been identified as a linoleic acid binding pocket.
Abstract: The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.
45 citations
TL;DR: Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX and a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion, indicating the presence of an allosteric binding site inhuman 5- LOX distinct from the ATP binding site.
30 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 3 |
| 2017 | 2 |
| 2016 | 1 |
| 2015 | 1 |
| 2014 | 1 |
| 2013 | 1 |