Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Kursula, Petri ; Flodin, Susanne ; Ehn, Maria ; Hammarström, Martin ; Schüler, Herwig LU orcid ; Nordlund, Pär and Stenmark, Pål LU orcid (2006) In Acta crystallographica. Section F, Structural biology communications 62(Pt 7). p.7-613
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Amino Acid Sequence, Antineoplastic Agents, Binding Sites, Carbon-Nitrogen Ligases/antagonists & inhibitors, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli/enzymology, Feedback, Humans, Models, Molecular, Molecular Sequence Data, Recombinant Proteins/chemistry
in
Acta crystallographica. Section F, Structural biology communications
volume
62
issue
Pt 7
pages
5 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:33745699187
  • pmid:16820675
ISSN
2053-230X
DOI
10.1107/S1744309106018136
language
English
LU publication?
no
id
332c4b7c-d234-48c4-a4b6-1c2bca915431
date added to LUP
2024-11-21 18:05:56
date last changed
2025-03-14 13:15:28
@article{332c4b7c-d234-48c4-a4b6-1c2bca915431,
  abstract     = {{<p>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.</p>}},
  author       = {{Kursula, Petri and Flodin, Susanne and Ehn, Maria and Hammarström, Martin and Schüler, Herwig and Nordlund, Pär and Stenmark, Pål}},
  issn         = {{2053-230X}},
  keywords     = {{Amino Acid Sequence; Antineoplastic Agents; Binding Sites; Carbon-Nitrogen Ligases/antagonists & inhibitors; Cloning, Molecular; Crystallography, X-Ray; Escherichia coli/enzymology; Feedback; Humans; Models, Molecular; Molecular Sequence Data; Recombinant Proteins/chemistry}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{Pt 7}},
  pages        = {{7--613}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Acta crystallographica. Section F, Structural biology communications}},
  title        = {{Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy}},
  url          = {{http://dx.doi.org/10.1107/S1744309106018136}},
  doi          = {{10.1107/S1744309106018136}},
  volume       = {{62}},
  year         = {{2006}},
}