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Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides.

ABSTRACT: PRMT1 is the predominant type I protein arginine methyltransferase in mammals and highly conserved among all eukaryotes. It is essential for early postimplantation development in mouse. Here we describe the crystal structure of rat PRMT1 in complex with the reaction product AdoHcy and a 19 residue substrate peptide containing three arginines. The results reveal a two-domain structure-an AdoMet binding domain and a barrel-like domain-with the active site pocket located between the two domains. Mutagenesis studies confirmed that two active site glutamates are essential for enzymatic activity, and that dimerization of PRMT1 is essential for AdoMet binding. Three peptide binding channels are identified: two are between the two domains, and the third is on the surface perpendicular to the strands forming the beta barrel.

SUBMITTER: Zhang X

PROVIDER: S-EPMC4030380 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides.

Zhang Xing X Cheng Xiaodong X

Structure (London, England : 1993) 20030501 5

PRMT1 is the predominant type I protein arginine methyltransferase in mammals and highly conserved among all eukaryotes. It is essential for early postimplantation development in mouse. Here we describe the crystal structure of rat PRMT1 in complex with the reaction product AdoHcy and a 19 residue substrate peptide containing three arginines. The results reveal a two-domain structure-an AdoMet binding domain and a barrel-like domain-with the active site pocket located between the two domains. Mu ...[more]

PMID: 12737817

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Protein Arginine Methyltransferase PRMT1 Is Essential for Palatogenesis.

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Protein arginine methyltransferase PRMT1 is essential for palatogenesis

Project description:We report that neural crest-specific deletion of Prmt1 caused craniofacial malformations including cleft palate.

2019-09-01 | GSE114894 | GEO

Loss of the major Type I arginine methyltransferase PRMT1 causes substrate scavenging by other PRMTs.

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Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes.

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