1xsa
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Structure of the nudix enzyme AP4A hydrolase from homo sapiens (E63A mutant)
OverviewOverview
Asymmetric diadenosine 5',5-P(1),P(4)-tetraphosphate (Ap(4)A), hydrolases play a major role in maintaining homeostasis by cleaving the, metabolite diadenosine tetraphosphate (Ap(4)A) back into ATP and AMP. The, NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase, have been solved in both the presence and absence of the product ATP. The, adenine moiety of the nucleotide predominantly binds in a ring stacking, arrangement equivalent to that observed in the x-ray structure of the, homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class, of enzymes, opening avenues for the exploration of specific therapeutics., Binding of ATP induces substantial conformational and dynamic changes that, were not observed in the C. elegans structure. In contrast to the C., elegans homologue, important side chains that play a major role in, substrate binding do not have to reorient to accommodate the ligand. This, may have important implications in the mechanism of substrate recognition, in this class of enzymes.
About this StructureAbout this Structure
1XSA is a Single protein structure of sequence from Homo sapiens. Active as Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical), with EC number 3.6.1.17 Full crystallographic information is available from OCA.
ReferenceReference
Structure and substrate-binding mechanism of human Ap4A hydrolase., Swarbrick JD, Buyya S, Gunawardana D, Gayler KR, McLennan AG, Gooley PR, J Biol Chem. 2005 Mar 4;280(9):8471-81. Epub 2004 Dec 13. PMID:15596429
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