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http://purl.uniprot.org/citations/12144783http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12144783http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12144783http://www.w3.org/2000/01/rdf-schema#comment"The human base excision repair enzyme hNTH1, a homologue of Escherichia coli endonuclease III (Nth), is a 36kDa DNA glycosylase with associated abasic (AP) lyase activity. It has significant sequence homology with Nth in its DNA-binding motifs and catalytic residues but possesses a unique amino (N)-terminal tail (residues 1-95). We investigated the structure and function of this tail. Controlled proteolysis cleaved hNTH1 into discrete fragments to generate a 25kDA core domain lacking the N-terminal 98 residues. Surprisingly, recombinant hNTH1 lacking 55, 72 or 80 residues from the N terminus had four-to fivefold higher activities than the full-length enzyme. Kinetic analysis at transition states revealed that release of the final product, an AP site with a 3'-nick, is the rate-limiting step in the multi-step reaction mediated by hNTH1. The N-terminal tail regulates its overall catalytic turnover by reducing this product release rate by five-to sevenfold without affecting either the glycosylase or AP lyase activities, or the steady-state equilibrium concentration of Schiff base intermediate, the covalent complex of hNTH1 and AP-site DNA formed after the base is excised. The inhibitory role of the N-terminal tail in catalytic turnover explains the low activity of hNTH1 compared to that of its E.coli homologue."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.org/dc/terms/identifier"doi:10.1016/s0022-2836(02)00623-x"xsd:string
http://purl.uniprot.org/citations/12144783http://purl.org/dc/terms/identifier"doi:10.1016/s0022-2836(02)00623-x"xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/author"Liu X."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/author"Liu X."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/author"Roy R."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/author"Roy R."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/name"J. Mol. Biol."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/name"J. Mol. Biol."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/pages"265-276"xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/pages"265-276"xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/title"Truncation of amino-terminal tail stimulates activity of human endonuclease III (hNTH1)."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/title"Truncation of amino-terminal tail stimulates activity of human endonuclease III (hNTH1)."xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/volume"321"xsd:string
http://purl.uniprot.org/citations/12144783http://purl.uniprot.org/core/volume"321"xsd:string
http://purl.uniprot.org/citations/12144783http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12144783
http://purl.uniprot.org/citations/12144783http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12144783
http://purl.uniprot.org/citations/12144783http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12144783
http://purl.uniprot.org/citations/12144783http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12144783
http://purl.uniprot.org/uniprot/P78549http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/12144783
http://purl.uniprot.org/uniprot/P78549#attribution-9A830AE4D531FCEAC6FE56C845FF2CFBhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/12144783