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Ubiquitin-activating enzymes, also known as E1 enzymes, catalyze the first step in the ubiquitination reaction, which (among other things) can target a protein for degradation via a proteasome. This covalent bond of ubiquitin or ubiquitin-like proteins to targeted proteins is a major mechanism for regulating protein function in eukaryotic ...
In chemistry, stereoselectivity [1] is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non-stereospecific creation of a new stereocenter or during a non-stereospecific transformation of a pre-existing one. [2]
A ubiquitin-activating enzyme, or E1, first activates the ubiquitin by covalently attaching the molecule to its active site cysteine residue. The activated ubiquitin is then transferred to an E2 cysteine. Once conjugated to ubiquitin, the E2 molecule binds one of several ubiquitin ligases or E3s via a structurally conserved binding region.
In the latter sense, the term stereospecific reaction is commonly misused to mean highly stereoselective reaction. Chiral synthesis is built on a combination of stereospecific transformations (for the interconversion of existing stereocenters) and stereoselective ones (for the creation of new stereocenters), where also the optical activity of a ...
Due to the clear correlation between abnormal neddylation and cancer, a neddylation inhibitor was developed. Pevonedistat or MLN4929 is the first neddylation E1 inhibitor being tested for several clinical trials in cancer patients, both as a monotherapy and in combination with other therapies.
The ubiquitylation reaction proceeds in three or four steps depending on the mechanism of action of the E3 ubiquitin ligase. In the conserved first step, an E1 cysteine residue attacks the ATP-activated C-terminal glycine on ubiquitin, resulting in a thioester Ub-S-E1 complex. The energy from ATP and diphosphate hydrolysis drives the formation ...
Key steps of the Schmid–Hofheinz approach included an initial Ohrloff stereoselective hydroboration/oxidation to establish the "off-ring" methyl stereocenter on the propene side chain; two sequential lithium-reagent mediated alkylations that introduced all needed carbon atoms and that were, together highly diastereoselective; and further ...
The P-type ATPases, also known as E 1-E 2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. [1] P-type ATPases are α-helical bundle primary transporters named based upon their ability to catalyze auto- (or self-) phosphorylation (hence P) of a key conserved aspartate residue within the pump and their energy source ...