3HZA

Crystal structure of dUTPase H145W mutant

Summary for 3HZA

• Entry DOI: 10.2210/pdb3hza/pdb
• Descriptor: Deoxyuridine 5'-triphosphate nucleotidohydrolase, MAGNESIUM ION, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: jelly roll, domain swapping, hydrolase, nucleotide metabolism
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 18838.17

Authors

Leveles, I.,Harmat, V.,Pecsi, I.,Toth, J.,Vertessy, B.G. (deposition date: 2009-06-23, release date: 2009-11-24, Last modification date: 2023-09-06)

Primary citation

Pecsi, I.,Leveles, I.,Harmat, V.,Vertessy, B.G.,Toth, J.
Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase.
Nucleic Acids Res., 38:7179-7186, 2010

PubMed Abstract: Aromatic interactions are well-known players in molecular recognition but their catalytic role in biological systems is less documented. Here, we report that a conserved aromatic stacking interaction between dUTPase and its nucleotide substrate largely contributes to the stabilization of the associative type transition state of the nucleotide hydrolysis reaction. The effect of the aromatic stacking on catalysis is peculiar in that uracil, the aromatic moiety influenced by the aromatic interaction is relatively distant from the site of hydrolysis at the alpha-phosphate group. Using crystallographic, kinetics, optical spectroscopy and thermodynamics calculation approaches we delineate a possible mechanism by which rate acceleration is achieved through the remote π-π interaction. The abundance of similarly positioned aromatic interactions in various nucleotide hydrolyzing enzymes (e.g. most families of ATPases) raises the possibility of the reported phenomenon being a general component of the enzymatic catalysis of phosphate ester hydrolysis.

PubMed: 20601405
DOI: 10.1093/nar/gkq584

Experimental method

X-RAY DIFFRACTION (1.2 Å)