Abstract
Thiamine monophosphate kinase (ThiL) catalyzes the last step of thiamine pyrophosphate (TPP) synthesis, the ATP-dependent phosphorylation of thiamine monophosphate (TMP) to thiamine pyrophosphate. We solved the structure of ThiL from the human pathogen A. baumanii in complex with a pair of substrates TMP and a non-hydrolyzable adenosine triphosphate analog, and in complex with a pair of products TPP and adenosine diphosphate. High resolution of the data and anomalous diffraction allows for a detailed description of the binding mode of substrates and products, and their metal environment. The structures further support a previously proposed in-line attack reaction mechanism and show a distinct variability of metal content of the active site.
Highlights
Edwards*, Jan Abendroth* Seattle Structural Genomics Center for Infectious Disease, Beryllium Discovery Acinetobacter baumanii is a member of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species), all of which have a high rate of antibiotic resistance, are opportunistic, and are responsible for a large number of hospital borne infections
We solved the structure of A. baumanii ThiL in complex with its substrates Thiamine monophosphate (TMP) / AMPPNP, and in complex with its products Thiamine pyrophosphate (TPP) / ADP
The structures highlight the path of the reaction, and a distinct variability of metal content
Summary
Edwards*, Jan Abendroth* Seattle Structural Genomics Center for Infectious Disease, Beryllium Discovery Acinetobacter baumanii is a member of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species), all of which have a high rate of antibiotic resistance, are opportunistic, and are responsible for a large number of hospital borne infections.
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