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PDBsum entry 2qb2
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References listed in PDB file
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Key reference
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Title
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Inactivation of escherichia coli l-Aspartate aminotransferase by (s)-4-Amino-4,5-Dihydro-2-Thiophenecarboxylic acid reveals "a tale of two mechanisms".
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Authors
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D.Liu,
E.Pozharski,
B.W.Lepore,
M.Fu,
R.B.Silverman,
G.A.Petsko,
D.Ringe.
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Ref.
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Biochemistry, 2007,
46,
10517-10527.
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PubMed id
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Abstract
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As a mechanism-based inactivator of PLP-enzymes,
(S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid (SADTA) was cocrystallized
with Escherichia coli aspartate aminotransferase (l-AspAT) at a series of pH
values ranging from 6 to 8. Five structural models with high resolution
(1.4-1.85 A) were obtained for l-AspAT-SADTA complexes at pH 6.0, 6.5, 7.0, 7.5,
and 8.0. Electron densities of the models showed that two different adducts had
formed in the active sites. One adduct was formed from SADTA covalently linked
to pyridoxal 5'-phosphate (PLP) while the other adduct was formed with the
inhibitor covalently linked to Lysine246,1 the active site lysine. Moreover,
there is a strong indication based on the electron densities that the occurrence
of the two adducts is pH dependent. We conclude that SADTA inactivates l-AspAT
via two different mechanisms based on the binding direction of the inactivator.
Additionally, the structural models also show pH dependence of the protein
structure itself, which provided detailed mechanistic implications for l-AspAT.
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