Cloning and characterisation of hAps1 and hAps2, human diadenosinepolyphosphate-metabolising Nudix hydrolases

Leslie, Nick R, McLennan, Alexander G ORCID: 0000-0002-8057-2222 and Safrany, Stephen T (2002) Cloning and characterisation of hAps1 and hAps2, human diadenosinepolyphosphate-metabolising Nudix hydrolases. BMC Biochemistry, 3 (1). p. 20.

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Abstract

Background: The human genome contains at least 18 genes for Nudix hydrolase enzymes. Many have similar functions to one another. In order to understand their roles in cell physiology, these proteins must be characterised. Results: We have characterised two novel human gene products, hAps1, encoded by the NUDT11 gene, and hAps2, encoded by the NUDT10 gene. These cytoplasmic proteins are members of the DIPP subfamily of Nudix hydrolases, and differ from each other by a single amino acid. Both metabolise diadenosine-polyphosphates and, weakly, diphosphoinositol polyphosphates. An apparent polymorphism of hAps1 has also been identified, which leads to the point mutation S39N. This has also been characterised. The favoured nucleotides were diadenosine 5′,5‴- pentaphosphate (kcat/Km = 11, 8 and 16 × 10 3M-1s-1 respectively for hAps1, hAps1-39N and hAps2) and diadenosine 5′,5‴-hexaphosphate (kcat/K m = 13, 14 and 11 × 103M-1s-1 respectively for hAps1, hAps1-39N and hAps2). Both hAps1 and hAps2 had pH optima of 8.5 and an absolute requirement for divalent cations, with manganese (II) being favoured. Magnesium was not able to activate the enzymes. Therefore, these enzymes could be acutely regulated by manganese fluxes within the cell. Conclusions: Recent gene duplication has generated the two Nudix genes, NUDT11 and NUDT10. We have characterised their gene products as the closely related Nudix hydrolases, hAps1 and hAps2. These two gene products complement the activity of previously described members of the DIPP family, and reinforce the concept that Ap5A and Ap6A act as intracellular messengers.

Item Type:	Article
Additional Information:	Published: 16 July 2002. 13 pages (page numbers not for citation purposes).
Uncontrolled Keywords:	human genome, Nudix hydrolase enzymes, cell physiology, Nudix genes, NUDT11, NUDT10, DIPP, Ap5A, Ap6A, intracellular messengers
Subjects:	?? Q1 ??
Divisions:	Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	01 Aug 2008 12:19
Last Modified:	16 Mar 2024 06:26
DOI:	10.1186/1471-2091-3-20
Publisher's Statement :	© 2002 Leslie et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2091/3/20
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URI:	https://livrepository.liverpool.ac.uk/id/eprint/794