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Single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) in <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K contributing to protein functional defects have been found to be associated with numerous human diseases, such as cardiovascular disease, maple syrup urine disease, type 2 diabetes, and neurological disease. <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K N94K is an identified missense mutant produced by one of the <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in the human <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K coding sequence. However, the effects of the N94K mutant on its activity and structural property have not been defined. Here, we performed a detailed enzymological study using steady\u2010state kinetics in the presence of <jats:styled-content style=\"fixed-case\">pNPP<\/jats:styled-content> or phospho\u2010peptide substrates and crystallographic analyses of the wild\u2010type and N94K <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K. The <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K\u2010N94K significantly impaired its Mg<jats:sup>2+<\/jats:sup>\u2010dependent catalytic activity and structural analysis demonstrated that the N94K mutation induced a conformational change in the key residue in coordinating the Mg<jats:sup>2+<\/jats:sup> in the active site. Specifically, three Mg<jats:sup>2+<\/jats:sup> were located in the active site of the <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K N94K instead of two Mg<jats:sup>2+<\/jats:sup> in the <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K wild\u00a0type. Therefore, our results provide a structure basis for the metal ion\u2010dependent <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1K\u2010N94K phosphatase activity.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14631-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14631","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T15:36:22Z","timestamp":1542641782000},"page":"550-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Crystal structure and catalytic activity of the <scp>PPM<\/scp>1K N94K mutant"],"prefix":"10.1111","volume":"148","author":[{"given":"Meisam Rostaminasab","family":"Dolatabad","sequence":"first","affiliation":[{"name":"Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u2010lu","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan Shandong China"},{"name":"Key Laboratory of Chemical Biology 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