Type I protein arginine methyltransferase

 

This eukaryotic enzyme catalyses the sequential dimethylation of one of the terminal guanidino nitrogen atoms in arginine residues, resulting in formation of asymmetric dimethylarginine residues.

 

Reference Protein and Structure

Sequence
Q63009 UniProt (2.1.1.319) IPR025799 (Sequence Homologues) (PDB Homologues)
Biological species
Rattus norvegicus (Norway rat) Uniprot
PDB
1or8 - Structure of the Predominant protein arginine methyltransferase PRMT1 (2.35 Å) PDBe PDBsum 1or8
Catalytic CATH Domains
2.70.160.11 CATHdb 3.40.50.150 CATHdb (see all for 1or8)
Click To Show Structure

Enzyme Reaction (EC:2.1.1.319)

S-adenosyl-L-methionine zwitterion
CHEBI:59789ChEBI
+
L-argininium residue
CHEBI:29965ChEBI
→
S-adenosyl-L-homocysteine zwitterion
CHEBI:57856ChEBI
+
N(omega),N(omega)-dimethyl-L-arginine(1+) residue
CHEBI:61897ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: PRMT1 (gene name), PRMT2 (gene name), PRMT3 (gene name), PRMT4 (gene name), PRMT6 (gene name), PRMT8 (gene name), RMT1 (gene name), CARM1 (gene name),

Enzyme Mechanism

Introduction

Type I PRMTs are known to catalyse the mono- and asymmetric dimethylation of Arg residues although it is unclear if they do this via (i) release the monomethylated species before rebinding it to facilitate the second methylation event, i.e., a distributive mechanism, or (ii) bind to its substrates such that mono- and dimethylation occur sequentially without the release of the monomethylated species, i.e., a processive mechanism.

Similar to histone lysine methyltransferases, methyl transfer proceeds through an SN2 mechanism. The proton elimination step after methyl transfer is hypothesised to occur through a His-Asp proton relay system

Catalytic Residues Roles

UniProt PDB* (1or8)
Asp51, His293 Asp51(38)A, His293(280)A Forms the proton relay chain that removes the proton(s) from the active site. proton shuttle (general acid/base)
Glu144, Glu153 Glu144(131)A, Glu153(140)A The negative charges on both E153 and E144 are critical for catalysis. Probably help activate and stabilise the substrate argenine. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Smith BC et al. (2009), Biochim Biophys Acta, 1789, 45-57. Chemical mechanisms of histone lysine and arginine modifications. DOI:10.1016/j.bbagrm.2008.06.005. PMID:18603028.
  2. Obianyo O et al. (2008), Biochemistry, 47, 10420-10427. Kinetic mechanism of protein arginine methyltransferase 1. DOI:10.1021/bi800904m. PMID:18771293.
  3. Osborne TC et al. (2007), Biochemistry, 46, 13370-13381. Protein arginine methyltransferase 1: positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis. DOI:10.1021/bi701558t. PMID:17960915.
  4. Zhang X et al. (2003), Structure, 11, 509-520. Structure of the Predominant Protein Arginine Methyltransferase PRMT1 and Analysis of Its Binding to Substrate Peptides. DOI:10.1016/s0969-2126(03)00071-6. PMID:12737817.
  5. Zhang X et al. (2000), EMBO J, 19, 3509-3519. Crystal structure of the conserved core of protein arginine methyltransferase PRMT3. DOI:10.1093/emboj/19.14.3509. PMID:10899106.

Step 1.

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Catalytic Residues Roles

Residue Roles
Glu144(131)A electrostatic stabiliser
Glu153(140)A electrostatic stabiliser
Asp51(38)A proton shuttle (general acid/base)
His293(280)A proton shuttle (general acid/base)

Chemical Components

Step 1.

Contributors

Alex Gutteridge, Craig Porter, Gemma L. Holliday