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Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy

Item Type:Article
Title:Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy
Creators Name:Kursula, P. and Flodin, S. and Ehn, M. and Hammarstroem, M. and Schueler, H. and Nordlund, P. and Stenmark, P.
Abstract:Cytidine triphosphate synthetase (CTPS) is a key enzyme in nucleic acid and phospholipid biosynthesis and its activity is increased in certain human cancers, making it a promising drug target. The crystal structure of the synthetase domain of human CTPS, which represents the first structure of a CTPS from an eukaryote, has been determined. The structure is homotetrameric and each active site is formed by three different subunits. Sulfate ions bound to the active sites indicate the positions of phosphate-binding sites for the substrates ATP and UTP and the feedback inhibitor CTP. Together with earlier structures of bacterial CTPS, the human CTPS structure provides an extended understanding of the structure-function relationship of CTPS-family members. The structure also serves as a basis for structure-based design of anti-proliferative inhibitors.
Keywords:Cytidine triphosphate synthetase, Anticancer therapy
Source:Acta Crystallographica Section F
Publisher:International Union of Crystallography
Page Range:613-617
Date:1 July 2006
Official Publication:https://doi.org/10.1107/S1744309106018136
PubMed:View item in PubMed

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