2H3E

Structure of wild-type E. coli Aspartate Transcarbamoylase in the presence of N-phosphonacetyl-L-isoasparagine at 2.3A resolution

Summary for 2H3E

• Entry DOI: 10.2210/pdb2h3e/pdb
• Related: 1D09
• Descriptor: Aspartate carbamoyltransferase catalytic chain, Aspartate carbamoyltransferase regulatory chain, (S)-4-AMINO-4-OXO-3-(2-PHOSPHONOACETAMIDO)BUTANOIC ACID, ... (5 entities in total)
• Functional Keywords: cooperativity, transferase
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 103600.55

Authors

Eldo, J.,Cardia, J.P.,O'Day, E.M.,Xia, J.,Tsuruta, H.,Kantrowitz, E.R. (deposition date: 2006-05-22, release date: 2006-10-17, Last modification date: 2023-08-30)

Primary citation

Eldo, J.,Cardia, J.P.,O'day, E.M.,Xia, J.,Tsuruta, H.,Kantrowitz, E.R.
N-Phosphonacetyl-l-isoasparagine a Potent and Specific Inhibitor of Escherichia coli Aspartate Transcarbamoylase.
J.Med.Chem., 49:5932-5938, 2006

PubMed 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.

PubMed: 17004708
DOI: 10.1021/jm0607294

Experimental method

X-RAY DIFFRACTION (2.3 Å)