The Active Site of Paracoccus denitrificans Aromatic Amino Acid Aminotransferase Has Contrary Properties: Flexibility and Rigidity

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• 作者：Akihiro Okamoto ; Seiji Ishii ; Ken Hirotsu ; and Hiroyuki Kagamiyama
• 刊名：Biochemistry
• 出版年：1999
• 出版时间：January 26, 1999
• 年：1999
• 卷：38
• 期：4
• 页码：1176 - 1184
• 全文大小：204K
• 年卷期：v.38,no.4(January 26, 1999)
• ISSN：1520-4995

文摘

Paracoccus denitrificans aromatic amino acid aminotransferase (EC 2.6.1.57; pdAroAT) bindswith a series of aliphatic monocarboxylates attached to the bulky hydrophobic groups. To analyze theproperties of the active site in this enzyme, we determined the tertiary structures of pdAroAT complexedwith nine different inhibitors. Comparison of these active site structures showed that the active site ofpdAroAT consists of two parts with contrary properties: rigidity and flexibility. The regions that interactwith the carboxylates and methylene chains of the inhibitors gave essentially the same structures amongthese complexes, exhibiting the rigid property, which would involve fixing the substrate at the properorientation for efficient catalysis. The region that interacts with the terminal hydrophobic groups of theinhibitors gave versatile structures according to the structures of the terminal groups, showing that thisregion is structurally flexible. This is mainly achieved by the conformational versatility of the side chainsof Asp15, Lys16, Asn142, Arg292*, and Ser296*. These residues formed in the active site hydrogenbond networks, which were adaptable for the structures of the terminal hydrophobic groups of the inhibitors,with a small deformation or partial destruction according to the shapes and sizes of the inhibitors. Theseobservations illustrate how the flexibility and rigidity in the active site can be used for the substratebinding and recognition.