Structures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms
| Autor: | John H. Elder, Enrico A. Stura, G.S. Prasad, C.D. Stout |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Feline immunodeficiency virus Protein Conformation Immunodeficiency Virus Feline Crystallography X-Ray Protein Structure Secondary Viral Proteins chemistry.chemical_compound Structural Biology DUTP pyrophosphatase Hydrolase Animals Nucleotide Pyrophosphatases chemistry.chemical_classification biology Chemistry Uracil General Medicine biology.organism_classification Crystallography Phosphodiester bond Cats Crystallization Deoxyuracil Nucleotides Sequence motif DNA |
| Zdroj: | Acta Crystallographica Section D Biological Crystallography. 56:1100-1109 |
| ISSN: | 0907-4449 |
| DOI: | 10.1107/s0907444900009197 |
| Popis: | dUTP pyrophosphatase (dUTPase) cleaves the alpha-beta phosphodiester of dUTP to form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and providing the substrate for thymine synthesis. Seven crystal structures of feline immunodeficiency virus (FIV) dUTPase in three crystal forms have been determined, including complexes with substrate (dUTP), product (dUMP) or inhibitor (dUDP) bound. The native enzyme has been refined at 1.40 A resolution in a hexagonal crystal form and at 2.3 A resolution in an orthorhombic crystal form. In the dUDP complex in a cubic crystal form refined at 2.5 A resolution, the C-terminal conserved P-loop motif is fully ordered. The analysis defines the roles of five sequence motifs in interaction with uracil, deoxyribose and the alpha-, beta- and gamma-phosphates. The enzyme utilizes adaptive recognition to bind the alpha- and beta-phosphates. In particular, the alpha-beta phosphodiester adopts an unfavorable eclipsed conformation in the presence of the P-loop. This conformation may be relevant to the mechanism of alpha-beta phosphodiester bond cleavage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text