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PDBsum entry 1mvx
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protein ligands metals links
Transferase PDB id
1mvx

 

 

 

 

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Contents
Protein chain
269 a.a. *
Ligands
SO4
Metals
_NI
_ZN ×3
Waters ×51
* Residue conservation analysis
PDB id:
1mvx
Name: Transferase
Title: Structure of the set domain histone lysine methyltransferase clr4
Structure: Cryptic loci regulator 4. Chain: a. Fragment: residues 192-490. Synonym: lysine methyltransferase clr4. Engineered: yes
Source: Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.216     R-free:   0.286
Authors: J.R.Min,X.Zhang,X.D.Cheng,S.I.S.Grewal,R.-M.Xu
Key ref:
J.Min et al. (2002). Structure of the SET domain histone lysine methyltransferase Clr4. Nat Struct Biol, 9, 828-832. PubMed id: 12389037 DOI: 10.1038/nsb860
Date:
26-Sep-02     Release date:   30-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O60016  (CLR4_SCHPO) -  Histone-lysine N-methyltransferase, H3 lysine-9 specific from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Seq:
Struc: 		490 a.a.
269 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.1.1.355  - [histone H3]-lysine(9) N-trimethyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-lysyl9-[histone H3] + 3 S-adenosyl-L-methionine = N6,N6,N6- trimethyl-L-lysyl9-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H+
L-lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L-methionine
 = N(6),N(6),N(6)- trimethyl-L-lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L-homocysteine
 + 3 × H(+)
   Enzyme class 2: E.C.2.1.1.366  - [histone H3]-N(6),N(6)-dimethyl-lysine(9) N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N6,N6-dimethyl-L-lysyl9-[histone H3] + S-adenosyl-L-methionine = N6,N6,N6-trimethyl-L-lysyl9-[histone H3] + S-adenosyl-L- homocysteine + H+
N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L-methionine
 = N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L- homocysteine
 + 3 × H(+)
   Enzyme class 3: E.C.2.1.1.367  - [histone H3]-lysine(9) N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-lysyl9-[histone H3] + S-adenosyl-L-methionine = N6-methyl-L- lysyl9-[histone H3] + S-adenosyl-L-homocysteine + H+
L-lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L-methionine
 = N(6)-methyl-L- lysyl(9)-[histone H3]
 + 3 × S-adenosyl-L-homocysteine
 + 3 × H(+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/nsb860 Nat Struct Biol 9:828-832 (2002)
PubMed id: 12389037  
 
 
Structure of the SET domain histone lysine methyltransferase Clr4.
J.Min, X.Zhang, X.Cheng, S.I.Grewal, R.M.Xu.
 
  ABSTRACT  
 
Methylation of histone H3 lysine 9 is an important component of the 'histone code' for heterochromatic gene silencing. The SET domain-containing Clr4 protein, a close relative of Su(var)3-9 proteins in higher eukaryotes, specifically methylates lysine 9 of histone H3 and is essential for silencing in Schizosaccharomyces pombe. Here we report the 2.3 A resolution crystal structure of the catalytic domain of Clr4. The structure reveals an overall fold rich in beta-strands, a potential active site consisting of a SAM-binding pocket, and a connected groove that could accommodate the binding of the N-terminal tail of histone H3. The pre-SET motif contains a triangular zinc cluster coordinated by nine cysteines distant from the active site, whereas the post-SET region is largely flexible but proximal to the active site. The structure provides insights into the architecture of SET domain histone methyltransferases and establishes a paradigm for further characterization of the Clr4 family of epigenetic regulators.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The active site. a, A CPK model showing the distribution of conserved residues. Identical and similar residues among the four proteins shown in Fig. 1a are shown in blue and magenta, respectively. The area enclosed in the dashed lines has the highest concentration of conserved residues. The model is viewed in the same orientation as in Fig. 2a. b, A surface representation of the structure. Red, blue and white indicate negatively charged, positively charged and neutral surface potentials. The structure is shown in the same orientation as in (a), and the same area is enclosed by a yellow dashed line. A blue arrow points to the cleft where Arg 406 resides. c, Stereo view of the conserved area shown in (a,b). The side chains of several conserved residues are shown as stick models (carbon, orange; nitrogen, blue; oxygen, red; sulfur, magenta) superimposed with a ribbon drawing of the structure as in Fig. 2a. Key residues are labeled. 		Figure 4.
Figure 4. Potential cofactor-binding cleft in the HMTase domain of Clr4. A top view of the structure shown in a surface representation. Arg 409 and Tyr 381 are located in a cleft connected to the active site.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 828-832) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20856808 B.D.Prasad, S.Goel, and P.Krishna (2010).
In silico identification of carboxylate clamp type tetratricopeptide repeat proteins in Arabidopsis and rice as putative co-chaperones of Hsp90/Hsp70.
  PLoS One, 5, e12761.  
20049756 C.Dalhoff, M.Hüben, T.Lenz, P.Poot, E.Nordhoff, H.Köster, and E.Weinhold (2010).
Synthesis of S-adenosyl-L-homocysteine capture compounds for selective photoinduced isolation of methyltransferases.
  Chembiochem, 11, 256-265.  
20974918 C.Xu, C.Bian, W.Yang, M.Galka, H.Ouyang, C.Chen, W.Qiu, H.Liu, A.E.Jones, F.MacKenzie, P.Pan, S.S.Li, H.Wang, and J.Min (2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
  Proc Natl Acad Sci U S A, 107, 19266-19271.
PDB codes: 3jpx 3jzg 3jzh 3jzn 3k26 3k27
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
20236310 M.S.Cosgrove, and A.Patel (2010).
Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
  FEBS J, 277, 1832-1842.  
19608767 A.Vaquero, and D.Reinberg (2009).
Calorie restriction and the exercise of chromatin.
  Genes Dev, 23, 1849-1869.  
18974185 G.Ding, P.Lorenz, M.Kreutzer, Y.Li, and H.J.Thiesen (2009).
SysZNF: the C2H2 zinc finger gene database.
  Nucleic Acids Res, 37, D267-D273.  
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.  
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.  
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.  
17327221 T.R.Porras-Yakushi, J.P.Whitelegge, and S.Clarke (2007).
Yeast ribosomal/cytochrome c SET domain methyltransferase subfamily: identification of Rpl23ab methylation sites and recognition motifs.
  J Biol Chem, 282, 12368-12376.  
17374386 X.Cheng, and X.Zhang (2007).
Structural dynamics of protein lysine methylation and demethylation.
  Mutat Res, 618, 102-115.  
16622709 J.Mis, S.S.Ner, and T.A.Grigliatti (2006).
Identification of three histone methyltransferases in Drosophila: dG9a is a suppressor of PEV and is required for gene silencing.
  Mol Genet Genomics, 275, 513-526.  
16512904 V.Krauss, A.Fassl, P.Fiebig, I.Patties, and H.Sass (2006).
The evolution of the histone methyltransferase gene Su(var)3-9 in metazoans includes a fusion with and a re-fission from a functionally unrelated gene.
  BMC Evol Biol, 6, 18.  
15898057 M.Biel, V.Wascholowski, and A.Giannis (2005).
Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes.
  Angew Chem Int Ed Engl, 44, 3186-3216.  
16086857 S.C.Dillon, X.Zhang, R.C.Trievel, and X.Cheng (2005).
The SET-domain protein superfamily: protein lysine methyltransferases.
  Genome Biol, 6, 227.  
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.  
15964846 Y.Yin, C.Liu, S.N.Tsai, B.Zhou, S.M.Ngai, and G.Zhu (2005).
SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and mono-methylates lysine 20.
  J Biol Chem, 280, 30025-30031.  
14970850 S.B.Hake, A.Xiao, and C.D.Allis (2004).
Linking the epigenetic 'language' of covalent histone modifications to cancer.
  Br J Cancer, 90, 761-769.  
15659850 Z.Zhao, and W.H.Shen (2004).
Plants contain a high number of proteins showing sequence similarity to the animal SUV39H family of histone methyltransferases.
  Ann N Y Acad Sci, 1030, 661-669.  
12540855 B.Xiao, C.Jing, J.R.Wilson, P.A.Walker, N.Vasisht, G.Kelly, S.Howell, I.A.Taylor, G.M.Blackburn, and S.J.Gamblin (2003).
Structure and catalytic mechanism of the human histone methyltransferase SET7/9.
  Nature, 421, 652-656.
PDB code: 1o9s
14675547 B.Xiao, J.R.Wilson, and S.J.Gamblin (2003).
SET domains and histone methylation.
  Curr Opin Struct Biol, 13, 699-705.  
12826405 H.L.Schubert, R.M.Blumenthal, and X.Cheng (2003).
Many paths to methyltransfer: a chronicle of convergence.
  Trends Biochem Sci, 28, 329-335.  
12917322 J.Landry, A.Sutton, T.Hesman, J.Min, R.M.Xu, M.Johnston, and R.Sternglanz (2003).
Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae.
  Mol Cell Biol, 23, 5972-5978.  
12628190 J.Min, Q.Feng, Z.Li, Y.Zhang, and R.M.Xu (2003).
Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.
  Cell, 112, 711-723.
PDB code: 1nw3
12567185 K.L.Manzur, A.Farooq, L.Zeng, O.Plotnikova, A.W.Koch, Sachchidanand, and M.M.Zhou (2003).
A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3.
  Nat Struct Biol, 10, 187-196.
PDB code: 1n3j
14502267 K.Zhao, X.Chai, A.Clements, and R.Marmorstein (2003).
Structure and autoregulation of the yeast Hst2 homolog of Sir2.
  Nat Struct Biol, 10, 864-871.
PDB code: 1q14
12819771 R.C.Trievel, E.M.Flynn, R.L.Houtz, and J.H.Hurley (2003).
Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT.
  Nat Struct Biol, 10, 545-552.
PDB codes: 1ozv 1p0y
12575990 R.Marmorstein (2003).
Structure of SET domain proteins: a new twist on histone methylation.
  Trends Biochem Sci, 28, 59-62.  
12514135 T.Kwon, J.H.Chang, E.Kwak, C.W.Lee, A.Joachimiak, Y.C.Kim, J.Lee, and Y.Cho (2003).
Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet.
  EMBO J, 22, 292-303.
PDB codes: 1n6a 1n6c
12887903 X.Zhang, Z.Yang, S.I.Khan, J.R.Horton, H.Tamaru, E.U.Selker, and X.Cheng (2003).
Structural basis for the product specificity of histone lysine methyltransferases.
  Mol Cell, 12, 177-185.
PDB code: 1peg
12447351 R.N.Dutnall, and J.M.Denu (2002).
Methyl magic and HAT tricks.
  Nat Struct Biol, 9, 888-891.  
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.

 

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