DFMO inhibitor mechanism

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Hbf878

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Praca własna

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https://plwiki.pl/b/23881

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528 x 262 Pixel (39288 Bytes)

Opis:

Mechanism for the inhibition of ornithine decarboxylase (ODC) by the irreversible inhibitor difluromethylornithine (DFMO a.k.a Eflornithine). E denotes the inhibited enzyme, Py denotes pyridoxal-5’-phosphate, which assists the transiminations in the first and 5th step. In trypanosoma, DFMO inhibition of ODC results in impaired Trypanothione metabolism. In mouse ODC, the lysine residue bound to Py and assisting in the mechanism (step 1 and 5) is Lys69 and the cysteine residue covalently modified by DFMO is Cys360. Cys360 is embedded in the sequence -WGPTCDGL(I)D-, which is common to all known eukaryote ODCs.

Note: In this image, all reactions are depicted as irreversible. In reality, the attachment and de-attachment of Py (steps 1 and 5) as well as the final tautomerization step are probably equilibrium reactions under physiological conditions, whereas the decarboxylation and removal of fluoride reactions are likely irreversible.

Reference: Poulin R, Lu L, Ackermann B, Bey P, Pegg AE (1992). "Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites". The Journal of Biological Chemistry 267 (1): 150–8. PMID 1730582.

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CC0

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Creative Commons Zero, Public Domain Dedication