Nudix hydrolase

Function

Nudix hydrolase (NDX) hydrolyses a wide range of organic pyrophosphatases including nucleoside di- and triphosphates, dinucleoside and diphosphoinositol polyphosphates, nucleotide sugars and RNA caps^[1]. In prokaryotes the number of Nudix genes varies from 0 to over 30. Mammals have around 24 Nudix genes. NDX proteins contain the GX5EX7REUXEEXGU signature sequence^[2]. An example of a well-studied Nudix enzyme is NudT16. Human NDX 16 is called U8-SNORNA-capping enzyme.

Nudix hydrolase 7 has a role in peroxisomal acyl-CoA homeostasis^[3].
Nudix hydrolase 15 is a negative regulator of thiopurine activation and toxicity.

Relevance

NDX 7 eliminates potentially toxic nucleotide metabolites from the cell. The NDX of E. coli is named MutT and is able to neutralize the promutagenic compound 7,8-dihydro-oxoguanosine triphosphate thus preventing its incorporation into DNA^[4].

Structural highlights

The structure contains the NDX signature sequence and ^[5]. Monomer A is colored deepskyblue, monomer B is colored salmon, water molecules are shown as red spheres.

3D structures of Nudix hydrolase

Nudix hydrolase 3D structures

Structure of Nudix hydrolase MutT complex with ATP and Mg+2 ion (green) (PDB entry 1su2)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ McLennan AG. The Nudix hydrolase superfamily. Cell Mol Life Sci. 2006 Jan;63(2):123-43. doi: 10.1007/s00018-005-5386-7. PMID:16378245 doi:http://dx.doi.org/10.1007/s00018-005-5386-7
↑ Sheikh S, O'Handley SF, Dunn CA, Bessman MJ. Identification and characterization of the Nudix hydrolase from the Archaeon, Methanococcus jannaschii, as a highly specific ADP-ribose pyrophosphatase. J Biol Chem. 1998 Aug 14;273(33):20924-8. PMID:9694840
↑ Reilly SJ, Tillander V, Ofman R, Alexson SE, Hunt MC. The nudix hydrolase 7 is an Acyl-CoA diphosphatase involved in regulating peroxisomal coenzyme A homeostasis. J Biochem. 2008 Nov;144(5):655-63. PMID:18799520 doi:10.1093/jb/mvn114
↑ McLennan AG. The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review). Int J Mol Med. 1999 Jul;4(1):79-89. PMID:10373642
↑ Ranatunga W, Hill EE, Mooster JL, Holbrook EL, Schulze-Gahmen U, Xu W, Bessman MJ, Brenner SE, Holbrook SR. Structural studies of the Nudix hydrolase DR1025 from Deinococcus radiodurans and its ligand complexes. J Mol Biol. 2004 May 21;339(1):103-16. PMID:15123424 doi:http://dx.doi.org/10.1016/j.jmb.2004.01.065

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Alexander Berchansky, Michal Harel, Tihitina Y Aytenfisu

[1] McLennan AG. The Nudix hydrolase superfamily. Cell Mol Life Sci. 2006 Jan;63(2):123-43. doi: 10.1007/s00018-005-5386-7. PMID:16378245 doi:http://dx.doi.org/10.1007/s00018-005-5386-7

[2] Sheikh S, O'Handley SF, Dunn CA, Bessman MJ. Identification and characterization of the Nudix hydrolase from the Archaeon, Methanococcus jannaschii, as a highly specific ADP-ribose pyrophosphatase. J Biol Chem. 1998 Aug 14;273(33):20924-8. PMID:9694840

[3] Reilly SJ, Tillander V, Ofman R, Alexson SE, Hunt MC. The nudix hydrolase 7 is an Acyl-CoA diphosphatase involved in regulating peroxisomal coenzyme A homeostasis. J Biochem. 2008 Nov;144(5):655-63. PMID:18799520 doi:10.1093/jb/mvn114

[4] McLennan AG. The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review). Int J Mol Med. 1999 Jul;4(1):79-89. PMID:10373642

[5] Ranatunga W, Hill EE, Mooster JL, Holbrook EL, Schulze-Gahmen U, Xu W, Bessman MJ, Brenner SE, Holbrook SR. Structural studies of the Nudix hydrolase DR1025 from Deinococcus radiodurans and its ligand complexes. J Mol Biol. 2004 May 21;339(1):103-16. PMID:15123424 doi:http://dx.doi.org/10.1016/j.jmb.2004.01.065

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