N-Phosphonacetyl-L-isoasparagine a Potent and Specific Inhibitor of Escherichia coli Aspartate Transcarbamoylase
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- 作者：Joby Eldo ; James P. Cardia ; Elizabeth M. O'Day ; Jiarong Xia ; Hiro Tsuruta ; Evan R. Kantrowitz
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：October 5, 2006
- 年：2006
- 卷：49
- 期：20
- 页码：5932 - 5938
- 全文大小：275K
- 年卷期：v.49,no.20(October 5, 2006)
- ISSN：1520-4804
文摘
The synthesis of a new inhibitor, N-phosphonacetyl-L-isoasparagine (PALI), of Escherichia coli aspartatetranscarbamoylase (ATCase) is reported, as well as structural studies of the enzyme·PALI complex. PALIwas synthesized in 7 steps from 
-benzyl L-aspartate. The KD of PALI was 2 
M. Kinetics and small-angleX-ray scattering experiments showed that PALI can induce the cooperative transition of ATCase from theT to the R state. The X-ray structure of the enzyme·PALI complex showed 22 hydrogen-bonding interactionsbetween the enzyme and PALI. The kinetic characterization and crystal structure of the ATCase·PALI complexalso provides detailed information regarding the importance of the 
-carboxylate for the binding of thesubstrate aspartate.
-benzyl L-aspartate. The KD of PALI was 2 M. Kinetics and small-angleX-ray scattering experiments showed that PALI can induce the cooperative transition of ATCase from theT to the R state. The X-ray structure of the enzyme·PALI complex showed 22 hydrogen-bonding interactionsbetween the enzyme and PALI. The kinetic characterization and crystal structure of the ATCase·PALI complexalso provides detailed information regarding the importance of the -carboxylate for the binding of thesubstrate aspartate.