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PDBsum entry 1yiy
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References listed in PDB file
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Key reference
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Title
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Crystal structures of aedes aegypti kynurenine aminotransferase.
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Authors
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Q.Han,
Y.G.Gao,
H.Robinson,
H.Ding,
S.Wilson,
J.Li.
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Ref.
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FEBS J, 2005,
272,
2198-2206.
[DOI no: ]
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PubMed id
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Abstract
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Aedes aegypti kynurenine aminotransferase (AeKAT) catalyzes the irreversible
transamination of kynurenine to kynurenic acid, the natural antagonist of NMDA
and 7-nicotinic acetycholine receptors. Here, we report the crystal structure of
AeKAT in its PMP and PLP forms at 1.90 and 1.55 A, respectively. The structure
was solved by a combination of single-wavelength anomalous dispersion and
molecular replacement approaches. The initial search model in the molecular
replacement method was built with the result of single-wavelength anomalous
dispersion data from the Br-AeKAT crystal in combination with homology modeling.
The solved structure shows that the enzyme is a homodimer, and that the two
subunits are stabilized by a number of hydrogen bonds, salts bridges, and
hydrophobic interactions. Each subunit is divided into an N-terminal arm and
small and large domains. Based on its folding, the enzyme belongs to the
prototypical fold type, aminotransferase subgroup I. The three-dimensional
structure shows a strictly conserved 'PLP-phosphate binding cup' featuring
PLP-dependent enzymes. The interaction between Cys284 (A) and Cys284 (B) is
unique in AeKAT, which might explain the cysteine effect of AeKAT activity.
Further mutation experiments of this residue are needed to eventually understand
the mechanism of the enzyme modulation by cysteine.
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Figure 3.
Fig. 3. Diagrams of 2F[o] – F[c] electron density maps
for the active sites of the PMP and PLP forms. The map contoured
at 2.0 sigma is calculated using data between 10.0 and 1.90
Å and 10.0 and 1.55 Å resolution for the PMP and PLP
forms of AeKAT, respectively. (A) PLP form; (B) PMP form.
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Figure 4.
Fig. 4. Schematic diagram showing active site interactions
in AeKAT. Hydrogen bonds are shown by dotted lines. Phe135 and
Val223 sandwich the pyridine ring of PLP. (A) PLP form; (B) PMP
form.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS J
(2005,
272,
2198-2206)
copyright 2005.
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