2HQU

Human dUTPase in complex with alpha,beta-iminodUTP and magnesium ion

Summary for 2HQU

• Entry DOI: 10.2210/pdb2hqu/pdb
• Descriptor: Deoxyuridine 5'-triphosphate nucleotidohydrolase, MAGNESIUM ION, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: jelly-roll, protein-substrate analogue ligand complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 2: Nucleus . Isoform 3: Mitochondrion : P33316
• Total number of polymer chains: 3
• Total formula weight: 54847.35

Authors

Barabas, O.,Varga, B.,Vertessy, B.G. (deposition date: 2006-07-19, release date: 2007-07-24, Last modification date: 2023-08-30)

Primary citation

Varga, B.,Barabas, O.,Kovari, J.,Toth, J.,Hunyadi-Gulyas, E.,Klement, E.,Medzihradszky, K.F.,Tolgyesi, F.,Fidy, J.,Vertessy, B.G.
Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase.
Febs Lett., 581:4783-4788, 2007

PubMed Abstract: Human dUTPase, essential for DNA integrity, is an important survival factor for cancer cells. We determined the crystal structure of the enzyme:alpha,beta-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 alpha-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.

PubMed: 17880943
DOI: 10.1016/j.febslet.2007.09.005

Experimental method

X-RAY DIFFRACTION (2.2 Å)