2vo1
CRYSTAL STRUCTURE OF THE SYNTHETASE DOMAIN OF HUMAN CTP SYNTHETASECRYSTAL STRUCTURE OF THE SYNTHETASE DOMAIN OF HUMAN CTP SYNTHETASE
Structural highlights
DiseasePYRG1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. A unique and recessive G to C mutation probably affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a complete loss of the expression of the protein.[1] FunctionPYRG1_HUMAN This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.[2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCytidine 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. Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy.,Kursula P, Flodin S, Ehn M, Hammarstrom M, Schuler H, Nordlund P, Stenmark P Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):613-7. Epub 2006 Jun 10. PMID:16820675[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||