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The Structure of Escherichia Coli PabC, Aminodeoxychorismate Lyase, and its Complex With D-Cycloserine

Published

Author(s)

Jane E. Ladner, Edward Eisenstein, K Fisher, P Y. Jensen, M Tordova, A J. Howard, G L. Gilliland

Abstract

The gene product of pabC, 4-amino-5-deoxychorismate (ADC) lyase, converts ADC to p-aminobenzoic acid (PABA) and pyruvate as part of the shikimic acid pathway leading to folic acid in Escherichia coli. ADC lyase is a homodimer of polypeptide chains of 269 residues and each polypeptide binds the cofactor pyridoxal 5'-phosphate (PLP). We report here the crystal structures of ADC lyase at 1.8- resolution and ADC lyase with D-cycloserine, at 2.3- resolution. The crystals belong to the space group P21212 with a single monomer in the asymmetric unit. Although the sequence homology shows only 24% identity, the structure of ADC lyase was solved by molecular replacement using the structure of D-amino acid aminotransferase, D-AAT, from Bacillus sphaericus as the beginning model. The final coordinates for ADC lyase have excellent geometry, a crystallographic R factor of 0.164 with an Rfree of 0.247. The structure includes the cofactor, PLP, which forms a Schiff base with Lys140 and has the same orientation in the active site pocket as the PLP in the structure of D-AAT [Peisach, D., Chipman, D.M., Van Ophem, P.W., Manning, J.M., and Ringe, D. (1998) Biochemistry 37, 4958-4967]. The structure of ADC lyase with D-cycloserine in the active site also has good geometry. We show that D-cycloserine is an inhibitor of ADC lyase and forms a Schiff base with the PLP. Steady state kinetic constants for ADC lyase are also reported and reveal a rather slow turnover. This work prepares the way for detailed structure/function studies of the protein encoded by pabC.
Citation
Biochemistry

Keywords

4-amino-5-deoxychorismate, 4-amino-5-deoxychorismate lyase, D-cycloserine, p-aminobenzolic acid, pabC, protein crystallography, protein structure, pyridoxal phosphate, shikimie acid pathway

Citation

Ladner, J. , Eisenstein, E. , Fisher, K. , Jensen, P. , Tordova, M. , Howard, A. and Gilliland, G. (2021), The Structure of Escherichia Coli PabC, Aminodeoxychorismate Lyase, and its Complex With D-Cycloserine, Biochemistry (Accessed May 22, 2024)

Issues

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Created October 12, 2021