User:Alexander Rudecki/Sandbox 1: Difference between revisions

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The cyclization reaction occurs via a nucleophilic attack of the α-amine on the γ carbon in the glutamine side chain. The enzymatic mechanism for DromeQC is still undetermined, but it seems plausible that it follows that of its human orthologue. In hQC, the N-terminus of the peptide substrate is inserted into the active site pocket, where the γ amide oxygen chelates the catalytic zinc ion<ref name="mechanism">PMID: 18470930</ref>. This ion-dipole interaction causes carbonyl polarization, making it a better electrophile. To facilitate the reaction, a conserved glutamate (Glu201) acts as both a general base and acid. Glu201 abstracts a proton from the α-amino group, causing it to nucleophilically attack the γ amide oxygen. This produces a tetrahedral intermediate with a charged oxygen that is stabilized by Zn<sup>2+</sup>. Glu201 then protonates the γ amide nitrogen, and an amine group is expelled as the carbonyl reforms. Also essential to this mechanism is a conserved aspartate (Asp248) that coordinates/stabilizes the leaving amine group.

==~~Location~~==

==Localization==

DromeQC is known to localize in the brain and peripheral nerves of ''D. melanogaster''<ref name="schilling"/>. This fact was unveiled by the discovery of adipokinetic hormone; this protein has an N-terminal pGlu, supporting a post translational modification via DromeQC<ref>PMID: 2117437</ref>. Adipokinetic hormone was found to localize in neurone and nerve endings by immunohistochemistry, suggesting that it functions as a locally released modulator in tissues such as heart and skeletal muscle<ref>PMID: 6342796</ref>. Thus, It has been suggested that DromeQC is part of the secretory pathway, being targeted to secretory vesicles where hormone maturation takes place<ref name="schilling"/>. This claim is supported by a 27 residue signal sequence contained at the N-terminus of DromeQC<ref name="schilling"/>. Further support stems from immunohistochemical evidence that DromeQC and its modified substrate are excreted from the cell, where they can be found in the extracellular medium<ref name="schilling"/>.

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 The cyclization reaction occurs via a nucleophilic attack of the α-amine on the γ carbon in the glutamine side chain. The enzymatic mechanism for DromeQC is still undetermined, but it seems plausible that it follows that of its human orthologue. In hQC, the N-terminus of the peptide substrate is inserted into the active site pocket, where the γ amide oxygen chelates the catalytic zinc ion<ref name="mechanism">PMID: 18470930</ref>. This ion-dipole interaction causes carbonyl polarization, making it a better electrophile. To facilitate the reaction, a conserved glutamate (Glu201) acts as both a general base and acid. Glu201 abstracts a proton from the α-amino group, causing it to nucleophilically attack the γ amide oxygen. This produces a tetrahedral intermediate with a charged oxygen that is stabilized by Zn<sup>2+</sup>. Glu201 then protonates the γ amide nitrogen, and an amine group is expelled as the carbonyl reforms. Also essential to this mechanism is a conserved aspartate (Asp248) that coordinates/stabilizes the leaving amine group.
-==Location==
+==Localization==
 DromeQC is known to localize in the brain and peripheral nerves of ''D. melanogaster''<ref name="schilling"/>. This fact was unveiled by the discovery of adipokinetic hormone; this protein has an N-terminal pGlu, supporting a post translational modification via DromeQC<ref>PMID: 2117437</ref>. Adipokinetic hormone was found to localize in neurone and nerve endings by immunohistochemistry, suggesting that it functions as a locally released modulator in tissues such as heart and skeletal muscle<ref>PMID: 6342796</ref>. Thus, It has been suggested that DromeQC is part of the secretory pathway, being targeted to secretory vesicles where hormone maturation takes place<ref name="schilling"/>. This claim is supported by a 27 residue signal sequence contained at the N-terminus of DromeQC<ref name="schilling"/>. Further support stems from immunohistochemical evidence that DromeQC and its modified substrate are excreted from the cell, where they can be found in the extracellular medium<ref name="schilling"/>.