Disease relevance of NUDT2

• The results reveal a high degree of functional conservation between lupin asymmetric Ap4A hydrolase and the 8-oxo-dGTP hydrolase from Escherichia coli [1].
• The APAH subfamily comprises enzymes or putative enzymes from such diverse microorganisms as Pseudomonas aeruginosa, Archaeoglobus fulgidus, and the actinomycete Mycoplana ramosa (formerly M. bullata) [2].
• Chronic hypoxic pulmonary arterial hypertension, APAH, and PPAH are characterized by vasoconstriction and vascular remodeling and are associated with decreased Kv currents in PA smooth muscle cells [3].

High impact information on NUDT2

• The high activity of Ap4A hydrolase in lanterns may be related to this ability and could be relevant to the use of the luciferase gene as a reporter gene [4].
• Enzymes hydrolyzing ApppA and/or AppppA in higher plants. Purification and some properties of diadenosine triphosphatase, diadenosine tetraphosphatase, and phosphodiesterase from yellow lupin (Lupinus luteus) seeds [5].
• Diadenosine tetraphosphatase, an enzyme splitting diadenosine tetraphosphate to AMP and ATP, has been purified to apparent homogeneity from a permanent cell line derived from a leukemic child [6].
• The structure represents the first Ap4A hydrolase to be determined, and sequence homology suggests that other members will have the same fold [7].
• Two regions of significant local similarity were identified between the Ap4A hydrolase and the histidine triad (HIT) protein family [Séraphin (1992) DNA Sequence 3, 177-179] [8].

Biological context of NUDT2

• The APAH1 gene encoding this Ap4A hydrolase has been mapped by fluorescence in situ hybridization and PCR to human chromosome 9p13 [9].

Anatomical context of NUDT2

• The study shows that leukocytes, platelets and erythrocytes all contain Ap4A hydrolase activity [10].
• Molecular cloning of diadenosine 5',5'''-P1,P4-tetraphosphate pyrophosphohydrolase (Ap4A hydrolase) from porcine small intestine: relationship to other enzymes of Ap4A catabolism [11].
• This article presents a fluorimetric study of the main properties of the enzymes dinucleoside tetraphosphate (asymmetrical) hydrolase or dinucleoside tetraphosphatase (Ap4Aase, EC 3.6.1.17) and dinucleoside triphosphate hydrolase or dinucleoside triphosphatase (Ap3Aase, EC 3.6.1.29), both present in adrenal medulla cytosolic extracts [12].

Associations of NUDT2 with chemical compounds

• Ap4Aase and Ap3Aase were assayed in cytosolic rat brain extracts using fluorogenic analogues of the respective substrates diadenosine tetraphosphate (Ap4A) and diadenosine triphosphate (Ap3A) [13].
• The cytosolic enzymes asymmetrical diadenosine tetraphosphate hydrolase (EC 3.6.1.17, Ap4Aase) and diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap3Aase) are inhibited competitively by suramin [13].
• Ki values for suramin as inhibitor of Ap4Aase and Ap3Aase were 5 x 10(-6) M and 3 x 10(-7) M, respectively [13].
• All four histidine residues which are conserved among the HIT proteins, including the HxHxH putative Zn(2+)-binding motif, are conserved in the Ap4A hydrolase [8].

Other interactions of NUDT2

• Given that the FHIT gene at 3p14.2, which encodes a diadenosine 5',5"'-P1,P3-triphosphate (AP3A) hydrolase, is a candidate tumor suppressor, APAH1 should also be considered a potential tumor suppressor [9].

Analytical, diagnostic and therapeutic context of NUDT2

• Ap4A hydrolase was partially purified from isolated human erythrocytes, leukocytes and platelets by high performance gel permeation chromatography and characterized by kinetic analysis and by probing immunoblots with an antibody raised against the human placental enzyme [10].

References