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PDBsum entry 3fvu
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Lyase, transferase
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PDB id
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3fvu
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References listed in PDB file
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Key reference
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Title
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Structural insight into the inhibition of human kynurenine aminotransferase i/glutamine transaminase k.
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Authors
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Q.Han,
H.Robinson,
T.Cai,
D.A.Tagle,
J.Li.
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Ref.
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J Med Chem, 2009,
52,
2786-2793.
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PubMed id
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Abstract
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Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of
kynurenic acid, a neuroactive compound. Here, we report three high-resolution
crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and
each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because
Tris is able to occupy the substrate binding position, we speculate that this
may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex
structure reveals that the binding moieties of the inhibitor are its indole ring
and a carboxyl group. Six chemicals with both binding moieties were tested for
their ability to inhibit hKAT I activity; 3-indolepropionic acid and
DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as
they cannot be considered as substrates of the enzyme, these two inhibitors are
promising candidates for future study. Perhaps even more significantly, we
report the discovery of two different ligands located simultaneously in the hKAT
I active center for the first time.
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