Nucleoside Triphosphate Pyrophosphohydrolase
Adenosine diphosphoribose pyrophosphatase
GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
GLU 82(Magnesium-1);ALA 66; (Magnesium-2)
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF NATIVE ENZYME, COMPLEX WITH ADP-RIBOSE, COMPLEX WITH GADOLINIUM.
The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family.
X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS), CATALYTIC MECHANISM.
Mechanism of the Escherichia coli ADP-ribose pyrophosphatase, a Nudix hydrolase.
The crystal structure and mutational analysis of human NUDT9.
Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis.
Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
Structures and mechanisms of Nudix hydrolases.
Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.
This enzyme belongs to Nudix (nucleoside diphosphate linked to x) hydrolase family. There are several types of ADP-ribose pyrophosphatases from various organisms (EzCatDB; S00814, S00921, S00923, S00924, D00880), in terms of substrate specificities, metal binding, active sites and reaction mechanisms. Although other homologous enzymes bind three metal ions, this enzyme binds only two magnesium ions, which corresponds to the magnesium-2 and magnesium-3 in the homologous enzymes. The magnesium numbering is based on the literature [5]. Magnesium-1 is bound to Glu82 and alpha-phosphate of ADP-ribose, whereas Magnesium-2 is bound to mainchain carbonyl of Ala66, Glu86 and both of the phosphate groups. The water that is bound to magnesium-1 is the nucleophile, which attacks on the alpha-phosphate of ADP-ribose. According to the literature [5] and [6], the reaction proceeds as follows: (0) A water molecule is bound to Magnesium-1. The magnesium ion may lower the pKa of the water molecule so that the water molecule can be a better nucleophile, and also stabilize the negative charge on the alpha-phosphate group. On the other hand, magnesium-2 that bridges the two phosphate groups may stabilize the negative charge of the leaving group, beta-phosphate. Moreover, Arg81 may modulate the activity of Glu82, which binds the magnesium-1. (1) Glu70 may act as a weak base to deprotonate the water molecule, forming a hydroxide ion. (2) The hydroxide ion makes a nucleophilic attack on the alpha-phosphate of ADP-ribose. (SN2-like reaction) (3) Arg54 and magnesium-2 may stabilize the negative charge on the leaving beta-phosphate group.