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PDBsum entry 2r5c
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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 mechanism of substrate specificity of aedes kynurenine aminotransferase.
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Authors
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Q.Han,
Y.G.Gao,
H.Robinson,
J.Li.
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Ref.
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Biochemistry, 2008,
47,
1622-1630.
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PubMed id
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Abstract
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Aedes aegypti kynurenine aminotransferase (AeKAT) is a multifunctional
aminotransferase. It catalyzes the transamination of a number of amino acids and
uses many biologically relevant alpha-keto acids as amino group acceptors. AeKAT
also is a cysteine S-conjugate beta-lyase. The most important function of AeKAT
is the biosynthesis of kynurenic acid, a natural antagonist of NMDA and
alpha7-nicotinic acetylcholine receptors. Here, we report the crystal structures
of AeKAT in complex with its best amino acid substrates, glutamine and cysteine.
Glutamine is found in both subunits of the biological dimer, and cysteine is
found in one of the two subunits. Both substrates form external aldemines with
pyridoxal 5-phosphate in the structures. This is the first instance in which one
pyridoxal 5-phosphate enzyme has been crystallized with cysteine or glutamine
forming external aldimine complexes, cysteinyl aldimine and glutaminyl aldimine.
All the units with substrate are in the closed conformation form, and the unit
without substrate is in the open form, which suggests that the binding of
substrate induces the conformation change of AeKAT. By comparing the active site
residues of the AeKAT-cysteine structure with those of the human KAT
I-phenylalanine structure, we determined that Tyr286 in AeKAT is changed to
Phe278 in human KAT I, which may explain why AeKAT transaminates hydrophilic
amino acids more efficiently than human KAT I does.
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