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Literature summary for 2.6.1.13 extracted from

  • Zhu, W.; Doubleday, P.F.; Catlin, D.S.; Weerawarna, P.M.; Butrin, A.; Shen, S.; Wawrzak, Z.; Kelleher, N.L.; Liu, D.; Silverman, R.B.
    A remarkable difference that one fluorine atom confers on the mechanisms of inactivation of human ornithine aminotransferase by two cyclohexene analogues of gamma-aminobutyric Acid (2020), J. Am. Chem. Soc., 142, 4892-4903 .
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid a nonselective aminotransferase inactivator Homo sapiens
(1S,3S)-3-amino-4-(1,1,1,3,3,3-hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid
-
Homo sapiens
(3S)-3-amino-4,4-difluorocyclohex-1-ene-1-carboxylic acid
-
Homo sapiens
(3S,4S)-3-amino-4-fluorocyclohex-1-ene-1-carboxylic acid
-
Homo sapiens
(4S,5S)-5-amino-4-fluorocyclohex-1-ene-1-carboxylic acid
-
Homo sapiens
(5S)-5-amino-4,4-difluorocyclohex-1-ene-1-carboxylic acid
-
Homo sapiens
(S)-vigabatrin
-
Homo sapiens
additional information design, synthesis, and evaluation of a series of fluorine-substituted cyclohexene analogues, as selective hOAT inhibitors, overview. Molecular dynamics simulations and electrostatic potential charge calculations are conducted to elucidated the significant influence of the one-fluorine difference on the corresponding intermediates, leading to two totally different inactivation pathways. Binding analysis of inhibitors 8 and 9 using the structure of hOAT (PDB ID 1OAT); inactivation mechanism, detailed overview. The compound shows enhanced potency, along with excellent selectivity over other aminotransferases. Enzyme binding structure analysis Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-ornithine + 2-oxoglutarate Homo sapiens
-
L-glutamate 5-semialdehyde + L-glutamate
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P04181
-
-

Source Tissue

Source Tissue Comment Organism Textmining
hepatoma cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-ornithine + 2-oxoglutarate
-
Homo sapiens L-glutamate 5-semialdehyde + L-glutamate
-
r

Subunits

Subunits Comment Organism
homodimer
-
Homo sapiens

Synonyms

Synonyms Comment Organism
hOAT
-
Homo sapiens
OAT
-
Homo sapiens
ornithine aminotransferase
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate PLP, dependent on Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0023
-
pH 8.0, temperature not specified in the publication Homo sapiens (3S)-3-amino-4,4-difluorocyclohex-1-ene-1-carboxylic acid
0.031
-
pH 8.0, temperature not specified in the publication Homo sapiens (3S,4S)-3-amino-4-fluorocyclohex-1-ene-1-carboxylic acid
0.065
-
pH 8.0, temperature not specified in the publication Homo sapiens (1S,3S)-3-amino-4-(1,1,1,3,3,3-hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid
0.54
-
pH 8.0, temperature not specified in the publication Homo sapiens (5S)-5-amino-4,4-difluorocyclohex-1-ene-1-carboxylic acid
1.4
-
pH 8.0, temperature not specified in the publication Homo sapiens (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid
4.38
-
pH 8.0, temperature not specified in the publication Homo sapiens (4S,5S)-5-amino-4-fluorocyclohex-1-ene-1-carboxylic acid

General Information

General Information Comment Organism
malfunction selective inhibition of hOAT has been shown to effectively suppress hepatocellular carcinoma (HCC) tumor growth in vivo Homo sapiens
physiological function human ornithine aminotransferase (hOAT), a pyridoxal 5'-phosphate-dependent enzyme, plays a critical role in the progression of hepatocellular carcinoma (HCC) and in the metabolic reprograming of HCC via proline and glutamine metabolic pathways Homo sapiens