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Crystal structures of thiamine monophosphate kinase from Acinetobacter baumannii in complex with substrates and products

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 substrate...

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Detalles Bibliográficos
Autores principales: Sullivan, Amy H., Dranow, David M., Horanyi, Peter S., Lorimer, Donald D., Edwards, Thomas E., Abendroth, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416309/
https://www.ncbi.nlm.nih.gov/pubmed/30867460
http://dx.doi.org/10.1038/s41598-019-40558-x
Descripción
Sumario: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.