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Transferase PDB id
1zkk
Jmol
Contents
Protein chains
160 a.a. *
Ligands
LYS-ARG-HIS-ARG-
LYS-VAL-LEU-ARG ×2
LYS-ARG-HIS-ARG-
LYS-VAL-LEU-ARG-
ASP ×2
SAH ×4
Waters ×1007
* Residue conservation analysis
PDB id:
1zkk
Name: Transferase
Title: Crystal structure of hset8 in ternary complex with h4 peptide (16-24) and adohcy
Structure: Histone-lysine n-methyltransferase, h4 lysine-20 specific. Chain: a, b, c, d. Fragment: sequence database residues 231-393. Synonym: histone h4-k20 methyltransferase, h4-k20-hmtase, set domain-containing protein 8, pr/set domain-containing protein 07, pr/set07, pr-set7, set8. Engineered: yes. Peptide corresponding to residues 15-24 of
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: set8, prset7, set07. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chain e, f, g, h are synthetic peptide from new england peptide corresponding to residue 15-24 of the
Biol. unit: Dimer (from PQS)
Resolution:
1.45Å     R-factor:   0.171     R-free:   0.199
Authors: J.-F.Couture,E.Collazo,J.S.Brunzelle,R.C.Trievel
Key ref: J.F.Couture et al. (2005). Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes Dev, 19, 1455-1465. PubMed id: 15933070 DOI: 10.1101/gad.1318405
Date:
03-May-05     Release date:   07-Jun-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9NQR1  (SETD8_HUMAN) -  N-lysine methyltransferase SETD8
Seq:
Struc: 		393 a.a.
160 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure

 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: 10.1101/gad.1318405 Genes Dev 19:1455-1465 (2005)
PubMed id: 15933070  
 
 
Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase.
J.F.Couture, E.Collazo, J.S.Brunzelle, R.C.Trievel.
 
  ABSTRACT  
 
SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine. Histone H4 intercalates in the substrate-binding cleft as an extended parallel beta-strand. Residues preceding Lys-20 in H4 engage in an extensive array of salt bridge, hydrogen bond, and van der Waals interactions with hSET8, while the C-terminal residues bind through predominantly hydrophobic interactions. Mutational analysis of both the substrate-binding cleft and histone H4 reveals that interactions with residues in the N and C termini of the H4 peptide are critical for conferring substrate specificity. Finally, analysis of the product specificity indicates that hSET8 is a monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  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.  
21243721 O.Binda, M.Boyce, J.S.Rush, K.K.Palaniappan, C.R.Bertozzi, and O.Gozani (2011).
A chemical method for labeling lysine methyltransferase substrates.
  Chembiochem, 12, 330-334.  
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.  
21220120 V.Avdic, P.Zhang, S.Lanouette, A.Groulx, V.Tremblay, J.Brunzelle, and J.F.Couture (2011).
Structural and biochemical insights into MLL1 core complex assembly.
  Structure, 19, 101-108.
PDB code: 3p4f
21282610 Z.Li, F.Nie, S.Wang, and L.Li (2011).
Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation.
  Proc Natl Acad Sci U S A, 108, 3116-3123.  
20703330 F.Pontvianne, T.Blevins, and C.S.Pikaard (2010).
Arabidopsis Histone Lysine Methyltransferases.
  Adv Bot Res, 53, 1.  
20084102 H.Wu, J.Min, V.V.Lunin, T.Antoshenko, L.Dombrovski, H.Zeng, A.Allali-Hassani, V.Campagna-Slater, M.Vedadi, C.H.Arrowsmith, A.N.Plotnikov, and M.Schapira (2010).
Structural biology of human H3K9 methyltransferases.
  PLoS One, 5, e8570.
PDB codes: 2igq 2o8j 2qpw 2r3a 2rfi 3hna
20512922 L.M.Congdon, S.I.Houston, C.S.Veerappan, T.M.Spektor, and J.C.Rice (2010).
PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression.
  J Cell Biochem, 110, 609-619.  
19556245 A.Patel, V.Dharmarajan, V.E.Vought, and M.S.Cosgrove (2009).
On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex.
  J Biol Chem, 284, 24242-24256.  
19234531 H.Yang, and C.A.Mizzen (2009).
The multiple facets of histone H4-lysine 20 methylation.
  Biochem Cell Biol, 87, 151-161.  
19818714 Q.Yan, S.Dutt, R.Xu, K.Graves, P.Juszczynski, J.P.Manis, and M.A.Shipp (2009).
BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response.
  Mol Cell, 36, 110-120.  
19721445 R.A.Copeland, M.E.Solomon, and V.M.Richon (2009).
Protein methyltransferases as a target class for drug discovery.
  Nat Rev Drug Discov, 8, 724-732.  
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.  
19706462 T.M.Spektor, and J.C.Rice (2009).
Identification and characterization of posttranslational modification-specific binding proteins in vivo by mammalian tethered catalysis.
  Proc Natl Acad Sci U S A, 106, 14808-14813.  
19398585 Y.H.Takahashi, J.S.Lee, S.K.Swanson, A.Saraf, L.Florens, M.P.Washburn, R.C.Trievel, and A.Shilatifard (2009).
Regulation of H3K4 trimethylation via Cps40 (Spp1) of COMPASS is monoubiquitination independent: implication for a Phe/Tyr switch by the catalytic domain of Set1.
  Mol Cell Biol, 29, 3478-3486.  
19250904 Y.Wang, B.Reddy, J.Thompson, H.Wang, K.Noma, J.R.Yates, and S.Jia (2009).
Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein.
  Mol Cell, 33, 428-437.  
18296440 H.Yang, J.J.Pesavento, T.W.Starnes, D.E.Cryderman, L.L.Wallrath, N.L.Kelleher, and C.A.Mizzen (2008).
Preferential dimethylation of histone H4 lysine 20 by Suv4-20.
  J Biol Chem, 283, 12085-12092.  
18840612 I.Kachirskaia, X.Shi, H.Yamaguchi, K.Tanoue, H.Wen, E.W.Wang, E.Appella, and O.Gozani (2008).
Role for 53BP1 Tudor domain recognition of p53 dimethylated at lysine 382 in DNA damage signaling.
  J Biol Chem, 283, 34660-34666.  
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
17967882 J.J.Pesavento, H.Yang, N.L.Kelleher, and C.A.Mizzen (2008).
Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle.
  Mol Cell Biol, 28, 468-486.  
18474616 J.K.Sims, and J.C.Rice (2008).
PR-Set7 establishes a repressive trans-tail histone code that regulates differentiation.
  Mol Cell Biol, 28, 4459-4468.  
18319261 M.S.Huen, S.M.Sy, J.M.van Deursen, and J.Chen (2008).
Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication.
  J Biol Chem, 283, 11073-11077.  
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.  
18693240 P.Joshi, E.A.Carrington, L.Wang, C.S.Ketel, E.L.Miller, R.S.Jones, and J.A.Simon (2008).
Dominant alleles identify SET domain residues required for histone methyltransferase of Polycomb repressive complex 2.
  J Biol Chem, 283, 27757-27766.  
18480059 S.I.Houston, K.J.McManus, M.M.Adams, J.K.Sims, P.B.Carpenter, M.J.Hendzel, and J.C.Rice (2008).
Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability.
  J Biol Chem, 283, 19478-19488.  
18391193 X.Zhang, and T.C.Bruice (2008).
Enzymatic mechanism and product specificity of SET-domain protein lysine methyltransferases.
  Proc Natl Acad Sci U S A, 105, 5728-5732.  
17227890 A.Sakaguchi, and R.Steward (2007).
Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.
  J Cell Biol, 176, 155-162.  
17562855 C.F.Sautel, D.Cannella, O.Bastien, S.Kieffer, D.Aldebert, J.Garin, I.Tardieux, H.Belrhali, and M.A.Hakimi (2007).
SET8-mediated methylations of histone H4 lysine 20 mark silent heterochromatic domains in apicomplexan genomes.
  Mol Cell Biol, 27, 5711-5724.  
17229421 D.Karachentsev, M.Druzhinina, and R.Steward (2007).
Free and chromatin-associated mono-, di-, and trimethylation of histone H4-lysine 20 during development and cell cycle progression.
  Dev Biol, 304, 46-52.  
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.  
18158331 M.Tardat, R.Murr, Z.Herceg, C.Sardet, and E.Julien (2007).
PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase.
  J Cell Biol, 179, 1413-1426.  
18166648 S.Jørgensen, I.Elvers, M.B.Trelle, T.Menzel, M.Eskildsen, O.N.Jensen, T.Helleday, K.Helin, and C.S.Sørensen (2007).
The histone methyltransferase SET8 is required for S-phase progression.
  J Cell Biol, 179, 1337-1345.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17388541 S.Wang, P.Hu, and Y.Zhang (2007).
Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9.
  J Phys Chem B, 111, 3758-3764.  
17374386 X.Cheng, and X.Zhang (2007).
Structural dynamics of protein lysine methylation and demethylation.
  Mutat Res, 618, 102-115.  
17707234 X.Shi, I.Kachirskaia, H.Yamaguchi, L.E.West, H.Wen, E.W.Wang, S.Dutta, E.Appella, and O.Gozani (2007).
Modulation of p53 function by SET8-mediated methylation at lysine 382.
  Mol Cell, 27, 636-646.  
16415881 J.F.Couture, E.Collazo, G.Hauk, and R.C.Trievel (2006).
Structural basis for the methylation site specificity of SET7/9.
  Nat Struct Mol Biol, 13, 140-146.
PDB code: 2f69
17070031 J.F.Couture, and R.C.Trievel (2006).
Histone-modifying enzymes: encrypting an enigmatic epigenetic code.
  Curr Opin Struct Biol, 16, 753-760.  
16624902 J.Shi, and R.K.Dawe (2006).
Partitioning of the maize epigenome by the number of methyl groups on histone H3 lysines 9 and 27.
  Genetics, 173, 1571-1583.  
17190600 M.V.Botuyan, J.Lee, I.M.Ward, J.E.Kim, J.R.Thompson, J.Chen, and G.Mer (2006).
Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair.
  Cell, 127, 1361-1373.
PDB codes: 2fhd 2g3r 2ig0
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 code is shown on the right.