SPOP oligomerization can serve to enhance SPOP-substrate avidity through the presentation of multiple substrate-binding MATH domains.
The interactions between substrates and inductors, and specially the preprotonation of the substrate by the adsorbed inductor, allow a preferential presentation of the substrate at the electrode surface.
The presentation of the substrate further explains the enigmatic latency of the protease, ensuring a single in cis cleavage.
The way of presentation of the substrate at the electrode, the working potential and the components of the electrical double layer, act also as determining factors.
For instance, the der1 homologue (derA, An01g00560), involved in transport of unfolded proteins out of the ER [ 54], is 4.0-fold induced; hrd3 (hrdC, An03g04600), involved in recognition and presentation of the substrate for degradation [ 55], is 3.3-fold induced.
The above sequences have a 9 10 amino acid insert (L1 inserts) that are believed to affect the presentation of the substrate to the neighboring catalytic triads in ClpP proteins and also known to contribute residues to putative lateral openings likely to stimulate or inhibit exit of peptide fragments from the core[ 52].
Thus, altered presentation of the APP substrate to γ-secretase, driven by either APP mutations or by binding of the pharmacological agents to APP could, in turn, allosterically affect PS1 conformation.
This may lead to severe respiratory failure, since bile acids increase the sPLA2 activity enabling the presentation of the phospholipid substrate to the catalytic site of the enzyme [ 45].
As a result, the difference in stereochemical outcome must arise from a reversed presentation of the β-ketoacyl substrate in the active site, exposing re or si faces of the β-keto group to NADPH.
Previously reported techniques for dual presentation of nanoscale morphologies on a single substrate typically require substrate modification or specialized equipment.
