FEBS letters, 2007-10, Vol.581 (24), p.4783-4788
2007
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Details
- Autor(en) / Beteiligte
- Titel
- Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase
- Ist Teil von
- FEBS letters, 2007-10, Vol.581 (24), p.4783-4788
- Ort / Verlag
- England: Elsevier B.V
- Erscheinungsjahr
- 2007
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Human dUTPase, essential for DNA integrity, is an important survival factor for cancer cells. We determined the crystal structure of the enzyme:α,β-imino-dUTP:Mg complex and performed equilibrium binding experiments in solution. Ordering of the C-terminus upon the active site induces close juxtaposition of the incoming nucleophile attacker water oxygen and the α-phosphorus of the substrate, decreasing their distance below the van der Waals limit. Complex interactions of the C-terminus with both substrate and product were observed via a specifically designed tryptophan sensor, suitable for further detailed kinetic and ligand binding studies. Results explain the key functional role of the C-terminus.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-5793eISSN: 1873-3468DOI: 10.1016/j.febslet.2007.09.005Titel-ID: cdi_proquest_miscellaneous_68306873
- Format
- –
- Schlagworte
- Amino Acid Sequence, Binding Sites, Catalysis, Crystallography, X-Ray, Enzyme mechanism, Flexible C-terminus, High-throughput screening for ligand binding, Humans, Initiation of catalysis, Ligands, Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Subunits - chemistry, Protein Subunits - genetics, Protein Subunits - metabolism, Pyrophosphatases - chemistry, Pyrophosphatases - genetics, Pyrophosphatases - metabolism, Tryptophan sensor