Structures of adenosine kinase from Trypanosoma brucei brucei

Jennifer Timm; Dolores González-Pacanowska; Keith S. Wilson

doi:10.1107/S2053230X13033621

Structures of adenosine kinase from Trypanosoma brucei brucei

Jennifer Timm, Dolores González-Pacanowska, Keith S. Wilson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Trypanosoma brucei is a single-cellular parasite of the genus Kinetoplastida and is the causative agent of African sleeping sickness in humans. Adenosine kinase is a key enzyme in the purine-salvage pathway, phosphorylating adenosine to AMP, and also activates cytotoxic analogues such as cordycepin and Ara-A by their phosphorylation. The structures of T. brucei brucei adenosine kinase (TbAK) in its unliganded open conformation and complexed with adenosine and ADP in the closed conformation are both reported to 2.6 Å resolution. The structures give insight into the binding mode of the substrates and the conformational change induced upon substrate binding. This information can be used to guide the improvement of cytotoxic substrate analogues as potential antitrypanosomal drugs.

Original language	English
Pages (from-to)	34-39
Number of pages	6
Journal	Acta Crystallographica Section F: Structural Biology and Crystallization Communications
Volume	70
Issue number	1
DOIs	https://doi.org/10.1107/S2053230X13033621
Publication status	Published - Jan 2014

Keywords

adenosine kinase
ligand complex
Trypanosoma brucei brucei

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10.1107/S2053230X13033621

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abstract = "Trypanosoma brucei is a single-cellular parasite of the genus Kinetoplastida and is the causative agent of African sleeping sickness in humans. Adenosine kinase is a key enzyme in the purine-salvage pathway, phosphorylating adenosine to AMP, and also activates cytotoxic analogues such as cordycepin and Ara-A by their phosphorylation. The structures of T. brucei brucei adenosine kinase (TbAK) in its unliganded open conformation and complexed with adenosine and ADP in the closed conformation are both reported to 2.6 {\AA} resolution. The structures give insight into the binding mode of the substrates and the conformational change induced upon substrate binding. This information can be used to guide the improvement of cytotoxic substrate analogues as potential antitrypanosomal drugs.",

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AB - Trypanosoma brucei is a single-cellular parasite of the genus Kinetoplastida and is the causative agent of African sleeping sickness in humans. Adenosine kinase is a key enzyme in the purine-salvage pathway, phosphorylating adenosine to AMP, and also activates cytotoxic analogues such as cordycepin and Ara-A by their phosphorylation. The structures of T. brucei brucei adenosine kinase (TbAK) in its unliganded open conformation and complexed with adenosine and ADP in the closed conformation are both reported to 2.6 Å resolution. The structures give insight into the binding mode of the substrates and the conformational change induced upon substrate binding. This information can be used to guide the improvement of cytotoxic substrate analogues as potential antitrypanosomal drugs.

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Structures of adenosine kinase from Trypanosoma brucei brucei

Abstract

Keywords

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