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Literature DB >> 17004708

N-phosphonacetyl-L-isoasparagine a potent and specific inhibitor of Escherichia coli aspartate transcarbamoylase.

Joby Eldo¹, James P Cardia, Elizabeth M O'Day, Jiarong Xia, Hiro Tsuruta, Evan R Kantrowitz.

Abstract

The synthesis of a new inhibitor, N-phosphonacetyl-L-isoasparagine (PALI), of Escherichia coli aspartate transcarbamoylase (ATCase) is reported, as well as structural studies of the enzyme.PALI complex. PALI was synthesized in 7 steps from beta-benzyl L-aspartate. The KD of PALI was 2 microM. Kinetics and small-angle X-ray scattering experiments showed that PALI can induce the cooperative transition of ATCase from the T to the R state. The X-ray structure of the enzyme.PALI complex showed 22 hydrogen-bonding interactions between the enzyme and PALI. The kinetic characterization and crystal structure of the ATCase.PALI complex also provides detailed information regarding the importance of the alpha-carboxylate for the binding of the substrate aspartate.

Entities: Chemical Gene Species

Mesh：

Substances：

Year: 2006 PMID： 17004708 PMCID： PMC2538380 DOI： 10.1021/jm0607294

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

30 in total

1. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

Authors: M M Bradford
Journal: Anal Biochem Date: 1976-05-07 Impact factor: 3.365

2. Selective inhibition of pyrimidine biosynthesis and effect on proliferative growth of colonic cancer cells.

Authors: K K Tsuboi; N H Edmunds; L K Kwong
Journal: Cancer Res Date: 1977-09 Impact factor: 12.701

3. Inhibition by N-(phosphonacetyl)-L-aspartate of aspartate transcarbamylase activity and drug-induced cell proliferation in mice.

Authors: T Yoshida; G R Stark; J Hoogenraad
Journal: J Biol Chem Date: 1974-11-10 Impact factor: 5.157

4. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.

Authors: U K Laemmli
Journal: Nature Date: 1970-08-15 Impact factor: 49.962

5. Synthetic studies of bacitracin. II. Synthesis of a cyclic dodecapeptide, an analogue of bacitracin A.

Authors: Y Ariyoshi; T Shiba; T Kaneko
Journal: Bull Chem Soc Jpn Date: 1967-11 Impact factor: 5.488

6. Aspartate transcarbamylase. Interaction with the transition state analogue N-(phosphonacetyl)-L-aspartate.

Authors: K D Collins; G R Stark
Journal: J Biol Chem Date: 1971-11 Impact factor: 5.157

7. Structure at 2.9-A resolution of aspartate carbamoyltransferase complexed with the bisubstrate analogue N-(phosphonacetyl)-L-aspartate.

Authors: K L Krause; K W Volz; W N Lipscomb
Journal: Proc Natl Acad Sci U S A Date: 1985-03 Impact factor: 11.205

8. Monitoring the transition from the T to the R state in E.coli aspartate transcarbamoylase by X-ray crystallography: crystal structures of the E50A mutant enzyme in four distinct allosteric states.

Authors: Kimberly Stieglitz; Boguslaw Stec; Darren P Baker; Evan R Kantrowitz
Journal: J Mol Biol Date: 2004-08-13 Impact factor: 5.469

9. Antitumor activity of N-(phosphonacetyl)-L-aspartic acid, a transition-state inhibitor of aspartate transcarbamylase.

Authors: R K Johnson; T Inouye; A Goldin; G R Stark
Journal: Cancer Res Date: 1976-08 Impact factor: 12.701

10. A fluorescent probe-labeled Escherichia coli aspartate transcarbamoylase that monitors the allosteric conformational state.

Authors: Jay M West; Hiro Tsuruta; Evan R Kantrowitz
Journal: J Biol Chem Date: 2003-10-26 Impact factor: 5.157

6 in total

N-phosphonacetyl-L-isoasparagine a potent and specific inhibitor of Escherichia coli aspartate transcarbamoylase.

1. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

2. Selective inhibition of pyrimidine biosynthesis and effect on proliferative growth of colonic cancer cells.

3. Inhibition by N-(phosphonacetyl)-L-aspartate of aspartate transcarbamylase activity and drug-induced cell proliferation in mice.

4. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.

5. Synthetic studies of bacitracin. II. Synthesis of a cyclic dodecapeptide, an analogue of bacitracin A.

6. Aspartate transcarbamylase. Interaction with the transition state analogue N-(phosphonacetyl)-L-aspartate.

7. Structure at 2.9-A resolution of aspartate carbamoyltransferase complexed with the bisubstrate analogue N-(phosphonacetyl)-L-aspartate.

8. Monitoring the transition from the T to the R state in E.coli aspartate transcarbamoylase by X-ray crystallography: crystal structures of the E50A mutant enzyme in four distinct allosteric states.

9. Antitumor activity of N-(phosphonacetyl)-L-aspartic acid, a transition-state inhibitor of aspartate transcarbamylase.

10. A fluorescent probe-labeled Escherichia coli aspartate transcarbamoylase that monitors the allosteric conformational state.

1. Design, synthesis, and bioactivity of novel inhibitors of E. coli aspartate transcarbamoylase.

Review 2. Allostery and cooperativity in Escherichia coli aspartate transcarbamoylase.

3. Submicromolar phosphinic inhibitors of Escherichia coli aspartate transcarbamoylase.

4. Synthesis and in vitro evaluation of aspartate transcarbamoylase inhibitors.

Review 5. From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases.

Review 6. Novel Highlight in Malarial Drug Discovery: Aspartate Transcarbamoylase.