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Transferase PDB id
2bqz
Jmol
Contents
Protein chains
161 a.a. *
Ligands
ARG-HIS-ARG-MLZ-
VAL-LEU-ARG-ASP-
ASN-TYR ×2
SAH ×2
Waters ×613
* Residue conservation analysis
PDB id:
2bqz
Name: Transferase
Title: Crystal structure of a ternary complex of the human histone methyltransferase pr-set7 (also known as set8)
Structure: Set8 protein. Chain: a, e. Fragment: set-domain, residues 192-352. Synonym: histone-lysine methyltransferase pr-set7. Engineered: yes. Histone h4. Chain: b, f. Fragment: residues 17-25
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606
Biol. unit: Dimer (from PDB file)
Resolution:
1.50Å     R-factor:   0.188     R-free:   0.206
Authors: B.Xiao,C.Jing,G.Kelly,P.A.Walker,F.W.Muskett,T.A.Frenkiel, S.R.Martin,K.Sarma,D.Reinberg,S.J.Gamblin,J.R.Wilson
Key ref: B.Xiao et al. (2005). Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev, 19, 1444-1454. PubMed id: 15933069 DOI: 10.1101/gad.1315905
Date:
28-Apr-05     Release date:   08-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.
161 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)
matches with 96.00% similarity 		+ 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.1315905 Genes Dev 19:1444-1454 (2005)
PubMed id: 15933069  
 
 
Specificity and mechanism of the histone methyltransferase Pr-Set7.
B.Xiao, C.Jing, G.Kelly, P.A.Walker, F.W.Muskett, T.A.Frenkiel, S.R.Martin, K.Sarma, D.Reinberg, S.J.Gamblin, J.R.Wilson.
 
  ABSTRACT  
 
Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.
 

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.  
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.  
20937900 H.Wei, and M.M.Zhou (2010).
Dimerization of a viral SET protein endows its function.
  Proc Natl Acad Sci U S A, 107, 18433-18438.
PDB codes: 3kma 3kmj 3kmt
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.  
21206904 L.W.Tsang, N.Hu, and D.A.Underhill (2010).
Comparative analyses of SUV420H1 isoforms and SUV420H2 reveal differences in their cellular localization and effects on myogenic differentiation.
  PLoS One, 5, e14447.  
20236310 M.S.Cosgrove, and A.Patel (2010).
Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
  FEBS J, 277, 1832-1842.  
20932471 T.Abbas, E.Shibata, J.Park, S.Jha, N.Karnani, and A.Dutta (2010).
CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation.
  Mol Cell, 40, 9.  
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.  
  18603028 B.C.Smith, and J.M.Denu (2009).
Chemical mechanisms of histone lysine and arginine modifications.
  Biochim Biophys Acta, 1789, 45-57.  
19017266 C.F.Sautel, P.Ortet, N.Saksouk, S.Kieffer, J.Garin, O.Bastien, and M.A.Hakimi (2009).
The histone methylase KMTox interacts with the redox-sensor peroxiredoxin-1 and targets genes involved in Toxoplasma gondii antioxidant defences.
  Mol Microbiol, 71, 212-226.  
19223465 H.Oda, I.Okamoto, N.Murphy, J.Chu, S.M.Price, M.M.Shen, M.E.Torres-Padilla, E.Heard, and D.Reinberg (2009).
Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development.
  Mol Cell Biol, 29, 2278-2295.  
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.  
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.  
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.  
18593478 C.S.Veerappan, Z.Avramova, and E.N.Moriyama (2008).
Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi.
  BMC Evol Biol, 8, 190.  
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.  
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.  
17218268 A.J.Ruthenburg, C.D.Allis, and J.Wysocka (2007).
Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark.
  Mol Cell, 25, 15-30.  
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.  
17712411 M.Frye, A.G.Fisher, and F.M.Watt (2007).
Epidermal stem cells are defined by global histone modifications that are altered by Myc-induced differentiation.
  PLoS ONE, 2, e763.  
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.  
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
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
16261189 C.Martin, and Y.Zhang (2005).
The diverse functions of histone lysine methylation.
  Nat Rev Mol Cell Biol, 6, 838-849.  
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.