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Unique utilization of a phosphoprotein phosphatase fold by a mammalian phosphodiesterase associated with WAGR syndrome.

Authors: Dermol, Ur┼íka  Janardan, Vishnu  Tyagi, Richa  Visweswariah, Sandhya S  Podobnik, Marjetka 
Citation: Dermol U, etal., J Mol Biol. 2011 Sep 23;412(3):481-94. doi: 10.1016/j.jmb.2011.07.060. Epub 2011 Jul 30.
Pubmed: (View Article at PubMed) PMID:21824479
DOI: Full-text: DOI:10.1016/j.jmb.2011.07.060

Metallophosphoesterase-domain-containing protein 2 (MPPED2) is a highly evolutionarily conserved protein with orthologs found from worms to humans. The human MPPED2 gene is found in a region of chromosome 11 that is deleted in patients with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, and MPPED2 may function as a tumor suppressor. However, the precise cellular roles of MPPED2 are unknown, and its low phosphodiesterase activity suggests that substrate hydrolysis may not be its prime function. We present here the structures of MPPED2 and two mutants, which show that the poor activity of MPPED2 is not only a consequence of the substitution of an active-site histidine residue by glycine but also due to binding of AMP or GMP to the active site. This feature, enhanced by structural elements of the protein, allows MPPED2 to utilize the conserved phosphoprotein-phosphatase-like fold in a unique manner, ensuring that its enzymatic activity can be combined with a possible role as a scaffolding or adaptor protein.

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CRRD Object Information
CRRD ID: 14397554
Created: 2019-04-10
Species: All species
Last Modified: 2019-04-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.