In:
Journal of Neurochemistry, Wiley, Vol. 148, No. 4 ( 2019-02), p. 550-560
Abstract:
Protein Phosphatase Mg 2+ /Mn 2+ ‐Dependent 1K ( PPM 1K),also named as PP 2Cm or branched‐chain α‐ketoacid dehydrogenase complex phosphatase, is a member of the metal‐dependent phosphatase family and an important metabolic regulator. Single nucleotide polymorphisms ( SNP s) in PPM 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. PPM 1K N94K is an identified missense mutant produced by one of the SNP s in the human PPM 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‐state kinetics in the presence of pNPP or phospho‐peptide substrates and crystallographic analyses of the wild‐type and N94K PPM 1K. The PPM 1K‐N94K significantly impaired its Mg 2+ ‐dependent catalytic activity and structural analysis demonstrated that the N94K mutation induced a conformational change in the key residue in coordinating the Mg 2+ in the active site. Specifically, three Mg 2+ were located in the active site of the PPM 1K N94K instead of two Mg 2+ in the PPM 1K wild type. Therefore, our results provide a structure basis for the metal ion‐dependent PPM 1K‐N94K phosphatase activity. image
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2019.148.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2020528-4
SSG:
12
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