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PDBsum entry 1ozv

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ozv
Jmol
Contents
Protein chains
429 a.a. *
Ligands
LYS ×3
SAH ×3
Waters ×644
* Residue conservation analysis
PDB id:
1ozv
Name: Transferase
Title: Crystal structure of the set domain of lsmt bound to lysine
Structure: Ribulose-1,5 bisphosphate carboxylase/oxygenase l subunit n-methyltransferase, chloroplast. Chain: a, b, c. Synonym: [ribulose-bisphosphate-carboxylase]-lysine n- methyltransferase, rubisco methyltransferase, rubisco lsmt, engineered: yes
Source: Pisum sativum. Pea. Organism_taxid: 3888. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Trimer (from PQS)
Resolution:
2.65Å     R-factor:   0.227     R-free:   0.266
Authors: R.C.Trievel,E.M.Flynn,R.L.Houtz,J.H.Hurley
Key ref:
R.C.Trievel et al. (2003). Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT. Nat Struct Biol, 10, 545-552. PubMed id: 12819771 DOI: 10.1038/nsb946
Date:
09-Apr-03     Release date:   01-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q43088  (RBCMT_PEA) -  Ribulose-1,5 bisphosphate carboxylase/oxygenase large subunit N-methyltransferase, chloroplastic
Seq:
Struc:
489 a.a.
429 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.2.1.1.127  - [Ribulose-bisphosphate carboxylase]-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3 S-adenosyl-L-methionine + [ribulose-bisphosphate carboxylase]-L-lysine = 3 S-adenosyl-L-homocysteine + [ribulose-bisphosphate carboxylase]- N6,N6,N6-trimethyl-L-lysine
3 × S-adenosyl-L-methionine
+ [ribulose-bisphosphate carboxylase]-L-lysine
Bound ligand (Het Group name = LYS)
matches with 60.00% similarity
=
3 × S-adenosyl-L-homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly
+ [ribulose-bisphosphate carboxylase]- N(6),N(6),N(6)-trimethyl-L-lysine
   Enzyme class 2: E.C.2.1.1.259  - [Fructose-bisphosphate aldolase]-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3 S-adenosyl-L-methionine + [fructose-bisphosphate aldolase]-L-lysine = 3 S-adenosyl-L-homocysteine + [fructose-bisphosphate aldolase]- N6,N6,N6-trimethyl-L-lysine
3 × S-adenosyl-L-methionine
+ [fructose-bisphosphate aldolase]-L-lysine
= 3 × S-adenosyl-L-homocysteine
+ [fructose-bisphosphate aldolase]- N(6),N(6),N(6)-trimethyl-L-lysine
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chloroplast   1 term 
  Biochemical function     [ribulose-bisphosphate carboxylase]-lysine N-methyltransferase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1038/nsb946 Nat Struct Biol 10:545-552 (2003)
PubMed id: 12819771  
 
 
Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT.
R.C.Trievel, E.M.Flynn, R.L.Houtz, J.H.Hurley.
 
  ABSTRACT  
 
SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet) to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase (LSMT) in ternary complexes with either lysine or epsilon-N-methyllysine (MeLys) and the product S-adenosylhomocysteine (AdoHcy) were determined to resolutions of 2.65 and 2.55 A, respectively. The zeta-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for S(N)2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys epsilon-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Stereochemical mechanism of methyl group transfer. (a) Model of the lysine -AdoMet substrate complex on the basis of the LSMT SET -Lys -AdoHcy complex. The formation of the nascent bond between the deprotonated N of the lysine and the C methyl group of AdoMet is denoted with a dashed line, and the geometry of S[N]2 reaction is shown with a black arc. (b) Model of the MeLys -AdoMet substrate complex based on the LSMT SET -MeLys -AdoHcy complex. The figure is labeled as in a.
Figure 5.
Figure 5. Comparison of hydrogen bonding in the active sites of LSMT and SET7/9. (a) Stereo view of the superimposition of the lysine-binding clefts of LSMT (blue) and the SET7/9 -histone H3 MeLys4 -AdoHcy ternary complex (PDB entry 1O9S) (red). Hydrogen bonds between the protein and -amino groups, and carbon-oxygen hydrogen bonds between the invariant Tyr and methyl groups are illustrated with dashed magenta lines. (b) Stereo view of the superimposition of the lysine-binding clefts of LSMT (blue) and the SET7/9 -AdoMet complex (PDB entry 1N6A) (green). Hydrogen bonds are illustrated as in a.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 545-552) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21131967 D.Levy, A.J.Kuo, Y.Chang, U.Schaefer, C.Kitson, P.Cheung, A.Espejo, B.M.Zee, C.L.Liu, S.Tangsombatvisit, R.I.Tennen, A.Y.Kuo, S.Tanjing, R.Cheung, K.F.Chua, P.J.Utz, X.Shi, R.K.Prinjha, K.Lee, B.A.Garcia, M.T.Bedford, A.Tarakhovsky, X.Cheng, and O.Gozani (2011).
Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling.
  Nat Immunol, 12, 29-36.  
21307598 D.W.Kim, K.B.Kim, J.Y.Kim, and S.B.Seo (2011).
Characterization of a novel histone H3K36 methyltransferase setd3 in zebrafish.
  Biosci Biotechnol Biochem, 75, 289-294.  
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.  
20670441 J.M.Zhou, E.Lee, F.Kanapathy-Sinnaiaha, Y.Park, J.A.Kornblatt, Y.Lim, and R.K.Ibrahim (2010).
Structure-function relationships of wheat flavone O-methyltransferase: Homology modeling and site-directed mutagenesis.
  BMC Plant Biol, 10, 156.  
20236310 M.S.Cosgrove, and A.Patel (2010).
Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
  FEBS J, 277, 1832-1842.  
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.  
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.  
  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.  
18210369 B.A.Manjasetty, A.P.Turnbull, S.Panjikar, K.Büssow, and M.R.Chance (2008).
Automated technologies and novel techniques to accelerate protein crystallography for structural genomics.
  Proteomics, 8, 612-625.  
18611379 H.Demirci, S.T.Gregory, A.E.Dahlberg, and G.Jogl (2008).
Multiple-site trimethylation of ribosomal protein L11 by the PrmA methyltransferase.
  Structure, 16, 1059-1066.
PDB codes: 3cjq 3cjr 3cjs 3cjt 3cju 3egv
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
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.  
17512990 D.W.Ng, T.Wang, M.B.Chandrasekharan, R.Aramayo, S.Kertbundit, and T.C.Hall (2007).
Plant SET domain-containing proteins: structure, function and regulation.
  Biochim Biophys Acta, 1769, 316-329.  
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.  
17589523 J.F.Couture, E.Collazo, P.A.Ortiz-Tello, J.S.Brunzelle, and R.C.Trievel (2007).
Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase.
  Nat Struct Mol Biol, 14, 689-695.
PDB codes: 2q8c 2q8d 2q8e
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.  
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.  
17291768 W.K.Paik, D.C.Paik, and S.Kim (2007).
Historical review: the field of protein methylation.
  Trends Biochem Sci, 32, 146-152.  
17374386 X.Cheng, and X.Zhang (2007).
Structural dynamics of protein lysine methylation and demethylation.
  Mutat Res, 618, 102-115.  
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
16600877 Z.Han, L.Guo, H.Wang, Y.Shen, X.W.Deng, and J.Chai (2006).
Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5.
  Mol Cell, 22, 137-144.
PDB codes: 2g99 2g9a
15933069 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, and J.R.Wilson (2005).
Specificity and mechanism of the histone methyltransferase Pr-Set7.
  Genes Dev, 19, 1444-1454.
PDB code: 2bqz
15590646 R.E.Collins, M.Tachibana, H.Tamaru, K.M.Smith, D.Jia, X.Zhang, E.U.Selker, Y.Shinkai, and X.Cheng (2005).
In vitro and in vivo analyses of a Phe/Tyr switch controlling product specificity of histone lysine methyltransferases.
  J Biol Chem, 280, 5563-5570.  
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.  
15485804 D.Patnaik, H.G.Chin, P.O.Estève, J.Benner, S.E.Jacobsen, and S.Pradhan (2004).
Substrate specificity and kinetic mechanism of mammalian G9a histone H3 methyltransferase.
  J Biol Chem, 279, 53248-53258.  
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
14675547 B.Xiao, J.R.Wilson, and S.J.Gamblin (2003).
SET domains and histone methylation.
  Curr Opin Struct Biol, 13, 699-705.  
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.