Calculation of the pKa Values for the Ligands and Side Chains of Escherichia coli d-Alanine:d-Alanine Ligase
- 29 December 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 42 (1) , 109-117
- https://doi.org/10.1021/jm980351c
Abstract
Poisson-Boltzmann electrostatics methods have been used to calculate the pKa shifts for the ligands and titratable side chains of D-alanine:D-alanine ligase of the ddlb gene of Escherichia coli (DdlB). The focus of this study is to determine the ionization state of the second D-alanine (D-Ala2) in the active site of DdlB. The pKa of the amine is shifted over 5 pKa units more alkaline in the protein, clearly implying that D-Ala2 is bound to DdlB in its zwitterionic state and not in the free-base form as had been previously suggested. Comparisons are made to the depsipeptide ligase from the vancomycin-resistance cascade, VanA. It is suggested that VanA has different enzymatic properties due to a change in binding specificity rather than altered catalytic behavior and that the specificity of binding D-lactate over D-Ala2 may arise from the difference in ionization characteristics of the ligands.Keywords
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