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Tyrosine 87 Is Vital for the Activity of Human Protein Arginine Methyltransferase 3 (PRMT3)

Tyrosine 87 Is Vital for the Activity of Human Protein Arginine Methyltransferase 3 (PRMT3)

Helena Handrkova, Jiri Petrak, Petr Halada, Dagmar Pospisilova, Radek Cmejla

Biochim Biophys Acta. 2011 Feb;1814(2):277-82.

PMID: 21059412

Abstract:

Protein arginine methyltransferase 3 (PRMT3) is a cytosolic enzyme that catalyzes the formation of mono- and asymmetric dimethyl arginines, with ribosomal protein (RP) S2 as its main in vivo substrate. The interplay of PRMT3-RPS2 homologs in yeast is important for regulating the ribosomal subunit ratio and assembly. Prmt3-null mice display slower embryonic growth and development, although this phenotype is milder than in mouse RP gene knockouts. Defects in ribosome maturation are the hallmark of Diamond-Blackfan anemia (DBA). Sequencing of the PRMT3 gene in patients from the Czech DBA registry revealed a heterozygous mutation encoding the Tyr87Cys substitution. Although later analysis excluded this mutation as the cause of disease, we anticipated that this substitution might be important for PRMT3 function and decided to study it in detail. Tyr87 resides in a highly conserved substrate binding domain and has been predicted to be phosphorylated. To address the impact of putative Tyr87 phosphorylation on PRMT3 properties, we constructed two additional PRMT3 variants, Tyr87Phe and Tyr87Glu PRMT3, mimicking non-phosphorylated and phosphorylated Tyr87, respectively. The Tyr87Cys and Tyr87Glu-PRMT3 variants had markedly decreased affinity to RPS2 and, consequently, reduced enzymatic activity compared to the wild-type enzyme. The activity of the Tyr87Phe-PRMT3 mutant remained unaffected. No evidence of Tyr87 phosphorylation was found using mass spectrometric analysis of purified PRMT3, although phosphorylation of serines 25 and 27 was observed. In conclusion, Tyr87 is important for the interaction between PRMT3 and RPS2 and for its full enzymatic activity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416083	PRMT3 human			Price

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