PDBsum entry 1or8

Go to PDB code: 
protein ligands links
Transferase PDB id
Protein chains
313 a.a. *
15 a.a.* *
10 a.a.* *
9 a.a.* *
PHE ×2
GLY ×5
ARG ×2
GOL ×2
Waters ×170
* Residue conservation analysis
* C-alpha coords only
PDB id:
Name: Transferase
Title: Structure of the predominant protein arginine methyltransfer
Structure: Protein arginine n-methyltransferase 1. Chain: a. Fragment: s14. Engineered: yes. Substrate peptide. Chain: b, c, d, e. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: hrmt1l2 or prmt1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chemically synthesized
Biol. unit: Pentamer (from PQS)
2.35Å     R-factor:   0.195     R-free:   0.254
Authors: X.Zhang,X.Cheng
Key ref:
X.Zhang and X.Cheng (2003). Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides. Structure, 11, 509-520. PubMed id: 12737817 DOI: 10.1016/S0969-2126(03)00071-6
12-Mar-03     Release date:   26-Aug-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q63009  (ANM1_RAT) -  Protein arginine N-methyltransferase 1
353 a.a.
313 a.a.
Protein chain
No UniProt id for this chain
Struc: 15 a.a.
Protein chain
No UniProt id for this chain
Struc: 10 a.a.
Protein chain
No UniProt id for this chain
Struc: 9 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: E.C.  - Histone-arginine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone]
+ arginine-[histone]
Bound ligand (Het Group name = SAH)
corresponds exactly
+ N(omega)-methyl-arginine-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   5 terms 
  Biological process     methylation   10 terms 
  Biochemical function     protein binding     13 terms  


    Added reference    
DOI no: 10.1016/S0969-2126(03)00071-6 Structure 11:509-520 (2003)
PubMed id: 12737817  
Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides.
X.Zhang, X.Cheng.
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.
  Selected figure(s)  
Figure 5.
Figure 5. Dimer Formation of PRMT1(A) Two ring-like dimers (related by a crystallographic 2-fold) connected by a surface C254 via a disulfide bond are shown with a difference electron density map contoured at 5.5s. The dimer is formed through the arm (blue) and the outer surface of AdoMet binding domain (green), as indicated. The AdoHcy (gray) is in a stick model.(B) Two opposite GRASP surfaces of PRMT1 dimer. The surface is colored red for negative, blue for positive, and white for neutral.(C) Two opposite GRASP surfaces of PRMT1 monomer. Dimerization is mediated through hydrophobic patches of the arm and the outer surface of AdoMet binding domain, as indicated.
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 509-520) copyright 2003.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21175895 O.Blifernez, L.Wobbe, K.Niehaus, and O.Kruse (2011).
Protein arginine methylation modulates light-harvesting antenna translation in Chlamydomonas reinhardtii.
  Plant J, 65, 119-130.  
19897492 D.Kim, J.Lee, D.Cheng, J.Li, C.Carter, E.Richie, and M.T.Bedford (2010).
Enzymatic activity is required for the in vivo functions of CARM1.
  J Biol Chem, 285, 1147-1152.  
20812326 D.Thomas, T.M.Lakowski, M.L.Pak, J.J.Kim, and A.Frankel (2010).
Förster resonance energy transfer measurements of cofactor-dependent effects on protein arginine N-methyltransferase homodimerization.
  Protein Sci, 19, 2141-2151.  
21085121 E.Weerapana, C.Wang, G.M.Simon, F.Richter, S.Khare, M.B.Dillon, D.A.Bachovchin, K.Mowen, D.Baker, and B.F.Cravatt (2010).
Quantitative reactivity profiling predicts functional cysteines in proteomes.
  Nature, 468, 790-795.  
20345902 K.Bonham, S.Hemmers, Y.H.Lim, D.M.Hill, M.G.Finn, and K.A.Mowen (2010).
Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production.
  FEBS J, 277, 2096-2108.  
20480486 O.Obianyo, C.P.Causey, T.C.Osborne, J.E.Jones, Y.H.Lee, M.R.Stallcup, and P.R.Thompson (2010).
A chloroacetamidine-based inactivator of protein arginine methyltransferase 1: design, synthesis, and in vitro and in vivo evaluation.
  Chembiochem, 11, 1219-1223.  
20091730 S.Castellano, C.Milite, R.Ragno, S.Simeoni, A.Mai, V.Limongelli, E.Novellino, I.Bauer, G.Brosch, A.Spannhoff, D.Cheng, M.T.Bedford, and G.Sbardella (2010).
Design, synthesis and biological evaluation of carboxy analogues of arginine methyltransferase inhibitor 1 (AMI-1).
  ChemMedChem, 5, 398-414.  
19858291 T.B.van Dijk, N.Gillemans, C.Stein, P.Fanis, J.Demmers, M.van de Corput, J.Essers, F.Grosveld, U.M.Bauer, and S.Philipsen (2010).
Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases.
  Mol Cell Biol, 30, 260-272.  
21080372 Y.I.Chang, S.W.Lin, Y.Y.Chiou, J.S.Sung, L.C.Cheng, Y.L.Lu, K.H.Sun, K.Chang, C.H.Lin, and W.J.Lin (2010).
Establishment of an ectopically expressed and functional PRMT1 for proteomic analysis of arginine-methylated proteins.
  Electrophoresis, 31, 3834-3842.  
19359250 A.Perreault, S.Gascon, A.D'Amours, J.M.Aletta, and F.Bachand (2009).
A Methyltransferase-independent Function for Rmt3 in Ribosomal Subunit Homeostasis.
  J Biol Chem, 284, 15026-15037.  
18773966 A.Spannhoff, W.Sippl, and M.Jung (2009).
Cancer treatment of the future: inhibitors of histone methyltransferases.
  Int J Biochem Cell Biol, 41, 4.  
18603028 B.C.Smith, and J.M.Denu (2009).
Chemical mechanisms of histone lysine and arginine modifications.
  Biochim Biophys Acta, 1789, 45-57.  
19170758 F.Herrmann, and F.O.Fackelmayer (2009).
Nucleo-cytoplasmic shuttling of protein arginine methyltransferase 1 (PRMT1) requires enzymatic activity.
  Genes Cells, 14, 309-317.  
19158082 K.Kölbel, C.Ihling, K.Bellmann-Sickert, I.Neundorf, A.G.Beck-Sickinger, A.Sinz, U.Kühn, and E.Wahle (2009).
Type I Arginine Methyltransferases PRMT1 and PRMT-3 Act Distributively.
  J Biol Chem, 284, 8274-8282.  
19150423 M.T.Bedford, and S.G.Clarke (2009).
Protein arginine methylation in mammals: who, what, and why.
  Mol Cell, 33, 1.  
19344311 Q.Fan, J.Miao, L.Cui, and L.Cui (2009).
Characterization of PRMT1 from Plasmodium falciparum.
  Biochem J, 421, 107-118.  
19085993 R.Heinke, A.Spannhoff, R.Meier, P.Trojer, I.Bauer, M.Jung, and W.Sippl (2009).
Virtual Screening and Biological Characterization of Novel Histone Arginine Methyltransferase PRMT1 Inhibitors.
  ChemMedChem, 4, 69-77.  
19300908 S.S.Wolf (2009).
The protein arginine methyltransferase family: an update about function, new perspectives and the physiological role in humans.
  Cell Mol Life Sci, 66, 2109-2121.  
19289494 Z.Yu, T.Chen, J.Hébert, E.Li, and S.Richard (2009).
A mouse PRMT1 null allele defines an essential role for arginine methylation in genome maintenance and cell proliferation.
  Mol Cell Biol, 29, 2982-2996.  
18495660 K.Fronz, S.Otto, K.Kölbel, U.Kühn, H.Friedrich, A.Schierhorn, A.G.Beck-Sickinger, A.Ostareck-Lederer, and E.Wahle (2008).
Promiscuous modification of the nuclear poly(A)-binding protein by multiple protein-arginine methyltransferases does not affect the aggregation behavior.
  J Biol Chem, 283, 20408-20420.  
18771293 O.Obianyo, T.C.Osborne, and P.R.Thompson (2008).
Kinetic mechanism of protein arginine methyltransferase 1.
  Biochemistry, 47, 10420-10427.  
18263580 T.M.Lakowski, and A.Frankel (2008).
A kinetic study of human protein arginine N-methyltransferase 6 reveals a distributive mechanism.
  J Biol Chem, 283, 10015-10025.  
18316480 X.Zhao, V.Jankovic, A.Gural, G.Huang, A.Pardanani, S.Menendez, J.Zhang, R.Dunne, A.Xiao, H.Erdjument-Bromage, C.D.Allis, P.Tempst, and S.D.Nimer (2008).
Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity.
  Genes Dev, 22, 640-653.  
17483287 A.E.McBride, C.Zurita-Lopez, A.Regis, E.Blum, A.Conboy, S.Elf, and S.Clarke (2007).
Protein arginine methylation in Candida albicans: role in nuclear transport.
  Eukaryot Cell, 6, 1119-1129.  
17005254 C.D.Krause, Z.H.Yang, Y.S.Kim, J.H.Lee, J.R.Cook, and S.Pestka (2007).
Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential.
  Pharmacol Ther, 113, 50-87.  
17601874 D.A.Pasternack, J.Sayegh, S.Clarke, and L.K.Read (2007).
Evolutionarily divergent type II protein arginine methyltransferase in Trypanosoma brucei.
  Eukaryot Cell, 6, 1665-1681.  
17426288 D.Y.Lee, I.Ianculescu, D.Purcell, X.Zhang, X.Cheng, and M.R.Stallcup (2007).
Surface-scanning mutational analysis of protein arginine methyltransferase 1: roles of specific amino acids in methyltransferase substrate specificity, oligomerization, and coactivator function.
  Mol Endocrinol, 21, 1381-1393.  
17711414 F.Scebba, M.De Bastiani, G.Bernacchia, A.Andreucci, A.Galli, and L.Pitto (2007).
PRMT11: a new Arabidopsis MBD7 protein partner with arginine methyltransferase activity.
  Plant J, 52, 210-222.  
17848568 I.Goulet, G.Gauvin, S.Boisvenue, and J.Côté (2007).
Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization.
  J Biol Chem, 282, 33009-33021.  
17925405 J.Sayegh, K.Webb, D.Cheng, M.T.Bedford, and S.G.Clarke (2007).
Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain.
  J Biol Chem, 282, 36444-36453.  
17882262 N.Troffer-Charlier, V.Cura, P.Hassenboehler, D.Moras, and J.Cavarelli (2007).
Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains.
  EMBO J, 26, 4391-4401.
PDB codes: 2oqb 3b3f 3b3g 3b3j
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17960915 T.C.Osborne, O.Obianyo, X.Zhang, X.Cheng, and P.R.Thompson (2007).
Protein arginine methyltransferase 1: positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis.
  Biochemistry, 46, 13370-13381.  
17882261 W.W.Yue, M.Hassler, S.M.Roe, V.Thompson-Vale, and L.H.Pearl (2007).
Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase.
  EMBO J, 26, 4402-4412.
PDB codes: 2v74 2v7e
16492668 A.Ostareck-Lederer, D.H.Ostareck, K.P.Rucknagel, A.Schierhorn, B.Moritz, S.Huttelmaier, N.Flach, L.Handoko, and E.Wahle (2006).
Asymmetric arginine dimethylation of heterogeneous nuclear ribonucleoprotein K by protein-arginine methyltransferase 1 inhibits its interaction with c-Src.
  J Biol Chem, 281, 11115-11125.  
16322096 C.Teyssier, C.Y.Ou, K.Khetchoumian, R.Losson, and M.R.Stallcup (2006).
Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators.
  Mol Endocrinol, 20, 1276-1286.  
16879614 D.O.Passos, G.C.Bressan, F.C.Nery, and J.Kobarg (2006).
Ki-1/57 interacts with PRMT1 and is a substrate for arginine methylation.
  FEBS J, 273, 3946-3961.  
16616479 F.Blanchet, B.T.Schurter, and O.Acuto (2006).
Protein arginine methylation in lymphocyte signaling.
  Curr Opin Immunol, 18, 321-328.  
17070031 J.F.Couture, and R.C.Trievel (2006).
Histone-modifying enzymes: encrypting an enigmatic epigenetic code.
  Curr Opin Struct Biol, 16, 753-760.  
16293633 R.Sgarra, J.Lee, M.A.Tessari, S.Altamura, B.Spolaore, V.Giancotti, M.T.Bedford, and G.Manfioletti (2006).
The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6.
  J Biol Chem, 281, 3764-3772.  
15964996 C.Teyssier, H.Ma, R.Emter, A.Kralli, and M.R.Stallcup (2005).
Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation.
  Genes Dev, 19, 1466-1473.  
16159886 F.Herrmann, J.Lee, M.T.Bedford, and F.O.Fackelmayer (2005).
Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo.
  J Biol Chem, 280, 38005-38010.  
16051612 J.Lee, J.Sayegh, J.Daniel, S.Clarke, and M.T.Bedford (2005).
PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family.
  J Biol Chem, 280, 32890-32896.  
15869391 X.Cheng, R.E.Collins, and X.Zhang (2005).
Structural and sequence motifs of protein (histone) methylation enzymes.
  Annu Rev Biophys Biomol Struct, 34, 267-294.  
15195996 A.Dong, L.Zhou, X.Zhang, S.Stickel, R.J.Roberts, and X.Cheng (2004).
Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions.
  Biol Chem, 385, 373-379.
PDB code: 1svu
15056663 D.Cheng, N.Yadav, R.W.King, M.S.Swanson, E.J.Weinstein, and M.T.Bedford (2004).
Small molecule regulators of protein arginine methyltransferases.
  J Biol Chem, 279, 23892-23899.  
15292170 K.Sawada, Z.Yang, J.R.Horton, R.E.Collins, X.Zhang, and X.Cheng (2004).
Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase.
  J Biol Chem, 279, 43296-43306.
PDB code: 1u2z
15044439 T.B.Miranda, M.Miranda, A.Frankel, and S.Clarke (2004).
PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity.
  J Biol Chem, 279, 22902-22907.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.