The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. 2004

Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW, UK.

dUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in its native conformation and as a complex with dUDP. These reveal a novel protein fold that displays no structural similarities to previously described dUTPases. The molecular unit is a dimer with two active sites. Nucleotide binding promotes extensive structural rearrangements, secondary structure remodeling, and rigid body displacements of 20 A or more, which effectively bury the substrate within the enzyme core for the purpose of hydrolysis. The molecular complex is a trapped enzyme-substrate arrangement which clearly demonstrates structure-induced specificity and catalytic potential. This enzyme is a novel dUTPase and therefore a potential drug target in the treatment of Chagas' disease.

UI MeSH Term Description Entries
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011755 Pyrophosphatases A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-. Pyrophosphatase
D003856 Deoxyuracil Nucleotides Uracil nucleotides which contain deoxyribose as the sugar moiety. Deoxyuridine Phosphates,Nucleotides, Deoxyuracil,Phosphates, Deoxyuridine
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining

Related Publications

Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
August 2007, Biochimie,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
June 2001, Acta crystallographica. Section D, Biological crystallography,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
March 2003, Journal of molecular biology,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
October 2007, Proteins,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
February 1992, Nature,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
May 1997, Structure (London, England : 1993),
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
January 1996, Proteins,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
March 2002, The Journal of biological chemistry,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
July 2001, The Journal of biological chemistry,
Maria Harkiolaki, and Eleanor J Dodson, and Victor Bernier-Villamor, and Johan P Turkenburg, and Dolores González-Pacanowska, and Keith S Wilson
January 2004, Biochemistry,
Copied contents to your clipboard!