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Transferase PDB id
2f69
Jmol
Contents
Protein chain
244 a.a. *
Ligands
ACE-SER-LYS-SER-
MLZ-ASP-ARG-LYS-
TYR
SAH
Waters ×472
* Residue conservation analysis
PDB id:
2f69
Name: Transferase
Title: Ternary complex of set7/9 bound to adohcy and a taf10 peptide
Structure: Histone-lysine n-methyltransferase, h3 lysine-4 specific set7. Chain: a. Synonym: histone h3-k4 methyltransferase, h3-k4-hmtase, set domain-containing protein 7, set9, set7/9. Engineered: yes. Taf10 peptide, acetyl-ser-lys-ser-mlz-asp-arg- lys-tyr-thr-leu. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: set7, kiaa1717. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: synthetic human taf10 peptide
Biol. unit: Dimer (from PQS)
Resolution:
1.30Å     R-factor:   0.150     R-free:   0.174
Authors: J.-F.Couture,E.Collazo,G.Hauk,R.C.Trievel
Key ref:
J.F.Couture et al. (2006). Structural basis for the methylation site specificity of SET7/9. Nat Struct Mol Biol, 13, 140-146. PubMed id: 16415881 DOI: 10.1038/nsmb1045
Date:
28-Nov-05     Release date:   17-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q8WTS6  (SETD7_HUMAN) -  Histone-lysine N-methyltransferase SETD7
Seq:
Struc: 		366 a.a.
244 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.43  - Histone-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone]
S-adenosyl-L-methionine
 + L-lysine-[histone]
 =
S-adenosyl-L-homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly 		+ N(6)-methyl-L-lysine-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1038/nsmb1045 Nat Struct Mol Biol 13:140-146 (2006)
PubMed id: 16415881  
 
 
Structural basis for the methylation site specificity of SET7/9.
J.F.Couture, E.Collazo, G.Hauk, R.C.Trievel.
 
  ABSTRACT  
 
Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone H3, the tumor suppressor p53 and the TBP-associated factor TAF10. To elucidate the determinants of its substrate specificity, we have solved the enzyme's structure bound to a TAF10 peptide and examined its ability to methylate histone H3, TAF10 and p53 substrates bearing either mutations or covalent modifications within their respective methylation sites. Collectively, our data reveal that SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target. We then used a sequence-based approach with this motif to identify novel substrates for this PKMT. Among the putative targets is TAF7, which is methylated at Lys5 by the enzyme in vitro. These results demonstrate the predictive value of the consensus motif in identifying novel substrates for SET7/9.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structures of SET7/9 in complex with TAF10, p53 and histone H3 peptides. (a) Stereo view of the simulated annealing |F[o]| - |F[c]| electron density omit map (contoured at 2.0 ) for the TAF10 Lys189me peptide (cyan carbons) bound within the substrate-binding cleft of SET7/9. (b) Schematic representation of the interactions between SET7/9 and TAF10. Residues in the enzyme that engage in key van der Waals contacts, hydrogen bonds or salt-bridge interactions with TAF10 are illustrated. Hydrogen bonds and salt-bridge interactions are denoted with dashed lines. Residues in TAF10 are labeled with the modified Schechter-Berger notation. (c,d) Schematic illustrations of SET7/9 bound to a p53 peptide (c; PDB entry 1XQH) and histone H3 (d; PDB entry 1O9S), shown as in b. The alternate conformation of the histone H3 Gln5 side chain, stabilized by crystal contacts with the C-terminus of the histone H3 peptide, is highlighted in red (d). 		Figure 2.
Figure 2. Comparison of the SET7/9 methylation sites in histone H3, TAF10 and p53. (a) Sequence alignment of the methylation sites of the three substrates. The Schechter-Berger nomenclature denoting each position with respect to the methylation site is listed in the upper row. The consensus recognition motif of SET7/9 is shown in the bottom row ( , small residue; K, methylation site; X, variable residue). (b) Michaelis-Menten plots of the initial velocity versus substrate concentration for the methylation of the 30-residue TAF10 (solid line), p53 (long dashed line) and histone H3 (short dashed line) peptides by full-length SET7/9.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 140-146) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21276944 A.Dhayalan, S.Kudithipudi, P.Rathert, and A.Jeltsch (2011).
Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase.
  Chem Biol, 18, 111-120.  
  21141727 A.K.Upadhyay, and X.Cheng (2011).
Dynamics of histone lysine methylation: structures of methyl writers and erasers.
  Prog Drug Res, 67, 107-124.  
21151202 G.R.Stark, Y.Wang, and T.Lu (2011).
Lysine methylation of promoter-bound transcription factors and relevance to cancer.
  Cell Res, 21, 375-380.  
21047797 L.Kaustov, H.Ouyang, M.Amaya, A.Lemak, N.Nady, S.Duan, G.A.Wasney, Z.Li, M.Vedadi, M.Schapira, J.Min, and C.H.Arrowsmith (2011).
Recognition and specificity determinants of the human cbx chromodomains.
  J Biol Chem, 286, 521-529.
PDB codes: 2l11 2l12 2l1b 3fdt 3gv6 3h91 3i90 3i91
21151116 P.O.Estève, Y.Chang, M.Samaranayake, A.K.Upadhyay, J.R.Horton, G.R.Feehery, X.Cheng, and S.Pradhan (2011).
A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability.
  Nat Struct Mol Biol, 18, 42-48.
PDB code: 3os5
21243713 S.Krishnan, S.Horowitz, and R.C.Trievel (2011).
Structure and function of histone H3 lysine 9 methyltransferases and demethylases.
  Chembiochem, 12, 254-263.  
20703330 F.Pontvianne, T.Blevins, and C.S.Pikaard (2010).
Arabidopsis Histone Lysine Methyltransferases.
  Adv Bot Res, 53, 1.  
20603083 H.Kontaki, and I.Talianidis (2010).
Lysine methylation regulates E2F1-induced cell death.
  Mol Cell, 39, 152-160.  
  20227666 S.Pagans, S.E.Kauder, K.Kaehlcke, N.Sakane, S.Schroeder, W.Dormeyer, R.C.Trievel, E.Verdin, M.Schnolzer, and M.Ott (2010).
The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription.
  Cell Host Microbe, 7, 234-244.  
20659682 T.J.Wigle, L.M.Provencher, J.L.Norris, J.Jin, P.J.Brown, S.V.Frye, and W.P.Janzen (2010).
Accessing protein methyltransferase and demethylase enzymology using microfluidic capillary electrophoresis.
  Chem Biol, 17, 695-704.  
21062871 T.Sahr, T.Adam, C.Fizames, C.Maurel, and V.Santoni (2010).
O-carboxyl- and N-methyltransferases active on plant aquaporins.
  Plant Cell Physiol, 51, 2092-2104.  
20160011 X.D.Yang, E.Tajkhorshid, and L.F.Chen (2010).
Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB.
  Mol Cell Biol, 30, 2170-2180.  
19381457 F.Lan, and Y.Shi (2009).
Epigenetic regulation: methylation of histone and non-histone proteins.
  Sci China C Life Sci, 52, 311-322.  
19112458 H.R.Hotz, and A.H.Peters (2009).
Protein demethylation required for DNA methylation.
  Nat Genet, 41, 10-11.  
19822661 J.N.Psathas, S.Zheng, S.Tan, and J.C.Reese (2009).
Set2-dependent K36 methylation is regulated by novel intratail interactions within H3.
  Mol Cell Biol, 29, 6413-6426.  
19656396 J.Vyas, R.J.Nowling, M.W.Maciejewski, S.Rajasekaran, M.R.Gryk, and M.R.Schiller (2009).
A proposed syntax for Minimotif Semantics, version 1.
  BMC Genomics, 10, 360.  
19216533 M.D.Huq, S.G.Ha, H.Barcelona, and L.N.Wei (2009).
Lysine methylation of nuclear co-repressor receptor interacting protein 140.
  J Proteome Res, 8, 1156-1167.  
  19684477 S.Pradhan, H.G.Chin, P.O.Estève, and S.E.Jacobsen (2009).
SET7/9 mediated methylation of non-histone proteins in mammalian cells.
  Epigenetics, 4, 383-387.  
19208805 S.Raunser, R.Magnani, Z.Huang, R.L.Houtz, R.C.Trievel, P.A.Penczek, and T.Walz (2009).
Rubisco in complex with Rubisco large subunit methyltransferase.
  Proc Natl Acad Sci U S A, 106, 3160-3165.  
18984737 T.G.Deering, T.Ogihara, A.P.Trace, B.Maier, and R.G.Mirmira (2009).
Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes.
  Diabetes, 58, 185-193.  
19434754 T.Gao, R.E.Collins, J.R.Horton, X.Zhang, R.Zhang, A.Dhayalan, R.Tamas, A.Jeltsch, and X.Cheng (2009).
The ankyrin repeat domain of Huntingtin interacting protein 14 contains a surface aromatic cage, a potential site for methyl-lysine binding.
  Proteins, 76, 772-777.
PDB code: 3eu9
  18581285 A.Scoumanne, and X.Chen (2008).
Protein methylation: a new mechanism of p53 tumor suppressor regulation.
  Histol Histopathol, 23, 1143-1149.  
18221488 G.Brosch, P.Loidl, and S.Graessle (2008).
Histone modifications and chromatin dynamics: a focus on filamentous fungi.
  FEMS Microbiol Rev, 32, 409-439.  
19088188 J.F.Couture, L.M.Dirk, J.S.Brunzelle, R.L.Houtz, and R.C.Trievel (2008).
Structural origins for the product specificity of SET domain protein methyltransferases.
  Proc Natl Acad Sci U S A, 105, 20659-20664.
PDB codes: 3f9w 3f9x 3f9y 3f9z
18471979 K.Subramanian, D.Jia, P.Kapoor-Vazirani, D.R.Powell, R.E.Collins, D.Sharma, J.Peng, X.Cheng, and P.M.Vertino (2008).
Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase.
  Mol Cell, 30, 336-347.
PDB codes: 3cbm 3cbo 3cbp
19043555 L.M.Johnson, J.A.Law, A.Khattar, I.R.Henderson, and S.E.Jacobsen (2008).
SRA-domain proteins required for DRM2-mediated de novo DNA methylation.
  PLoS Genet, 4, e1000280.  
18311969 P.Hu, S.Wang, and Y.Zhang (2008).
How do SET-domain protein lysine methyltransferases achieve the methylation state specificity? Revisited by Ab initio QM/MM molecular dynamics simulations.
  J Am Chem Soc, 130, 3806-3813.  
18650421 Y.Li, M.A.Reddy, F.Miao, N.Shanmugam, J.K.Yee, D.Hawkins, B.Ren, and R.Natarajan (2008).
Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation.
  J Biol Chem, 283, 26771-26781.  
18208619 Z.Liang, R.P.Wong, L.H.Li, H.Jiang, H.Xiao, and G.Li (2008).
Development of pan-specific antibody against trimethyllysine for protein research.
  Proteome Sci, 6, 2.  
17517655 H.B.Guo, and H.Guo (2007).
Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity.
  Proc Natl Acad Sci U S A, 104, 8797-8802.  
  18072589 P.Rathert, X.Cheng, and A.Jeltsch (2007).
Continuous enzymatic assay for histone lysine methyltransferases.
  Biotechniques, 43, 602, 604, 606 passim.  
17635932 R.Magnani, N.R.Nayak, M.Mazarei, L.M.Dirk, and R.L.Houtz (2007).
Polypeptide substrate specificity of PsLSMT. A set domain protein methyltransferase.
  J Biol Chem, 282, 27857-27864.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17374386 X.Cheng, and X.Zhang (2007).
Structural dynamics of protein lysine methylation and demethylation.
  Mutat Res, 618, 102-115.  
16946699 A.Schuetz, A.Allali-Hassani, F.Martín, P.Loppnau, M.Vedadi, A.Bochkarev, A.N.Plotnikov, C.H.Arrowsmith, and J.Min (2006).
Structural basis for molecular recognition and presentation of histone H3 by WDR5.
  EMBO J, 25, 4245-4252.
PDB codes: 2gnq 2h9l 2h9m 2h9n 2h9o 2h9p 2o9k
16682405 J.F.Couture, G.Hauk, M.J.Thompson, G.M.Blackburn, and R.C.Trievel (2006).
Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases.
  J Biol Chem, 281, 19280-19287.
PDB codes: 2h21 2h23 2h2e 2h2j
17070031 J.F.Couture, and R.C.Trievel (2006).
Histone-modifying enzymes: encrypting an enigmatic epigenetic code.
  Curr Opin Struct Biol, 16, 753-760.  
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.