5EDD

Crystal structure of Mycobacterium tuberculosis dUTPase R140K, H145W mutant

5EDD の概要

• エントリーDOI: 10.2210/pdb5edd/pdb
• 関連するPDBエントリー: 2PY4 3H6D 3HZA 3I93 3LOJ 4GCY
• 分子名称: Deoxyuridine 5'-triphosphate nucleotidohydrolase, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: jelly-roll, enzyme-ligand complex, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18625.97

構造登録者

Nagy, G.N.,Leveles, I.,Lopata, A.,Harmat, V.,Toth, J.,Vertessy, G.B. (登録日: 2015-10-21, 公開日: 2016-11-02, 最終更新日: 2024-01-10)

主引用文献

Nagy, G.N.,Suardiaz, R.,Lopata, A.,Ozohanics, O.,Vekey, K.,Brooks, B.R.,Leveles, I.,Toth, J.,Vertessy, B.G.,Rosta, E.
Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases.
J. Am. Chem. Soc., 138:15035-15045, 2016

PubMed Abstract: Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the γ-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases.

PubMed: 27740761
DOI: 10.1021/jacs.6b09012

実験手法

X-RAY DIFFRACTION (1.97 Å)