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Literature summary for 2.3.2.23 extracted from

  • Morreale, F.E.; Bortoluzzi, A.; Chaugule, V.K.; Arkinson, C.; Walden, H.; Ciulli, A.
    Allosteric targeting of the Fanconi anemia ubiquitin-conjugating enzyme Ube2T by fragment screening (2017), J. Med. Chem., 60, 4093-4098 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.2.23

Application

Application Comment Organism
drug development enzyme Ube2T represents an attractive target for the development of inhibitors. Modulation of DNA repair pathways is a strategy for the development of inhibitors of tumor cell growth, as it can either potentiate the effects of radiotherapy and conventional genotoxins or exploit synthetic lethal interactions Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
Ube2T in complex with inhibitor 1-(1,3-benzothiazol-2-yl)methanamine, X-ray diffraction crystal structure analysis, PDB ID 5NGZ Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1-(1,3-benzothiazol-2-yl)methanamine i.e. EM04, about 40% inhibition of FANCD2 ubiquination Homo sapiens
2-amino-5-phenylfuran-3-carbonitrile i.e. EM11, about 25% inhibition of FANCD2 ubiquination Homo sapiens
3-methyl-3,4-dihydroquinazolin-2(1H)-one i.e. EM09, about 15% inhibition of FANCD2 ubiquination Homo sapiens
4-phenyl-1,3-thiazol-2-amine i.e. EM17, about 60% inhibition of FANCD2 ubiquination Homo sapiens
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide i.e. EM02, almost complete inhibition of FANCD2 ubiquination Homo sapiens
additional information identification of an allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro. One-dimensional 1H NMR spectroscopy, binding site identification through protein-observed NMR spectroscopy, and X-ray crystallography, overview. No inhibition by 5-(pyridin-2-yl)thiophene-2-carboxamide (EM29) Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine Homo sapiens
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 [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NPD8
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-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell Ube2T is overexpressed in several cancers Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
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 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
-
 ?

Synonyms

Synonyms Comment Organism
Ube2J1
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 Homo sapiens
UBE2T
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 Homo sapiens
ubiquitin-conjugating enzyme
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 Homo sapiens

General Information

General Information Comment Organism
metabolism Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway Homo sapiens
additional information the catalytic cysteine is C86 Homo sapiens
physiological function Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway. Together with FANCL (the E3 ligase), Ube2T catalyzes the monoubiquitination of the heterodimeric FANCI/FANCD2 complex, which is the key signaling event to activate the FA pathway for DNA repair Homo sapiens