PDBsum entry 1mj9

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Transferase PDB id
Protein chain
273 a.a. *
Waters ×73
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of yeast esa1(c304s) mutant complexed with a
Structure: Esa1 protein. Chain: a. Fragment: histone acetyltransferase domain (residues 160-44 synonym: esa1 histone acetyltransferase. Engineered: yes. Mutation: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: yor244w. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PQS)
2.50Å     R-factor:   0.232     R-free:   0.255
Authors: Y.Yan,S.Harper,D.Speicher,R.Marmorstein
Key ref:
Y.Yan et al. (2002). The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate. Nat Struct Biol, 9, 862-869. PubMed id: 12368900 DOI: 10.1038/nsb849
27-Aug-02     Release date:   30-Oct-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q08649  (ESA1_YEAST) -  Histone acetyltransferase ESA1
445 a.a.
273 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Histone acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [histone] = CoA + acetyl-[histone]
+ [histone]
Bound ligand (Het Group name = COA)
corresponds exactly
+ acetyl-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     transferase activity, transferring acyl groups other than amino-acyl groups     1 term  


    Added reference    
DOI no: 10.1038/nsb849 Nat Struct Biol 9:862-869 (2002)
PubMed id: 12368900  
The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate.
Y.Yan, S.Harper, D.W.Speicher, R.Marmorstein.
Yeast ESA1 is a member of the MYST subfamily of histone acetyltransferases (HATs), which use acetyl-coenzyme A (CoA) to acetylate specific Lys residues within histones to regulate gene expression. The structure of an ESA1-CoA complex reveals structural similarity to the catalytic core of the GCN5/PCAF subfamily of HAT proteins. Here we report additional structural and functional studies on ESA1 that demonstrate that histone acetylation proceeds through an acetyl-cysteine enzyme intermediate. This Cys residue is strictly conserved within the MYST members, suggesting a common mode of catalysis by this HAT subfamily. However, this mode of catalysis differs dramatically from the GCN5/PCAF subfamily, which mediate direct nucleophilic attack of the acetyl-CoA cofactor by the enzyme-deprotonated substrate lysine of the histone. These results demonstrate that different HAT subfamilies can use distinct catalytic mechanisms, which have implications for their distinct biological roles and for the development of HAT-specific inhibitors.
  Selected figure(s)  
Figure 2.
Figure 2. Structure at the active site of wild type and mutant ESA1 proteins. a, The structure of the ESA1(C304S)−CoA complex is shown with oxygen atoms colored red; nitrogen atoms, blue; carbon atoms, gray; and sulfur atoms, yellow. A sodium ion bound to CoA is pink, and a water molecule interacting with Ser 304 is aqua. A SIGMAA^45-weighted F[o] - F[c] omit map was generated by omitting residues within a 5 Å radius around the triad (Ser 304, Glu 338 and sulfur atom of CoA), followed by simulated annealing dynamics refinement at a temperature of 1,500 K. The map is contoured at 1.5 . b, The structure of the ESA1(WT)−CoA complex is shown using the same color coding and omit map generation as described in (a). The sulfenic acid oxidized form of Cys 304 is modeled in this structure and labeled as O-Cys 304. c, The structure of the ESA1(WT)−Ac-CoA complex is shown using the same color coding and omit map generation as described in (a). d, The structure of the ESA1(E338Q)−Ac-CoA complex is shown using the same color coding and omit map generation as described in (a). The sulfenic acid oxidized form of Cys 304 is modeled in this structure and labeled as O-Cys 304. e, Overlay of the structure and electron density map of Cys 304 in the acetylated and sulfenic acid oxidized form from the ESA1(WT)−Ac-CoA (red) and ESA1(E338Q)−Ac-CoA (blue) structures are shown, respectively.
Figure 4.
Figure 4. Proposed catalytic mechanism for histone acetylation by ESA1. ESA1 residues are blue (Glu 338 and Cys 304), Ac-CoA is red and the histone substrate is green. Water molecules that may function to shuttle protons between the enzyme, Ac-CoA and substrate are omitted here.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 862-869) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21217699 J.Kadlec, E.Hallacli, M.Lipp, H.Holz, J.Sanchez-Weatherby, S.Cusack, and A.Akhtar (2011).
Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1.
  Nat Struct Mol Biol, 18, 142-149.
PDB codes: 2y0m 2y0n
21132344 V.Sapountzi, and J.Côté (2011).
MYST-family histone acetyltransferases: beyond chromatin.
  Cell Mol Life Sci, 68, 1147-1156.  
21062452 A.H.Schiemann, F.Li, V.M.Weake, E.J.Belikoff, K.C.Klemmer, S.A.Moore, and M.J.Scott (2010).
Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila.
  BMC Mol Biol, 11, 80.  
18603028 B.C.Smith, and J.M.Denu (2009).
Chemical mechanisms of histone lysine and arginine modifications.
  Biochim Biophys Acta, 1789, 45-57.  
19819149 H.S.Mellert, and S.B.McMahon (2009).
Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells.
  Trends Biochem Sci, 34, 571-578.  
19473964 M.M.Brent, A.Iwata, J.Carten, K.Zhao, and R.Marmorstein (2009).
Structure and Biochemical Characterization of Protein Acetyltransferase from Sulfolobus solfataricus.
  J Biol Chem, 284, 19412-19419.
PDB code: 3f8k
19056256 C.E.Berndsen, and J.M.Denu (2008).
Catalysis and substrate selection by histone/protein lysine acetyltransferases.
  Curr Opin Struct Biol, 18, 682-689.  
18184660 D.Shi, V.Sagar, Z.Jin, X.Yu, L.Caldovic, H.Morizono, N.M.Allewell, and M.Tuchman (2008).
The crystal structure of N-acetyl-L-glutamate synthase from Neisseria gonorrhoeae provides insights into mechanisms of catalysis and regulation.
  J Biol Chem, 283, 7176-7184.
PDB codes: 2r8v 2r98 3b8g
18753131 E.L.Mersfelder, and M.R.Parthun (2008).
Involvement of Hat1p (Kat1p) catalytic activity and subcellular localization in telomeric silencing.
  J Biol Chem, 283, 29060-29068.  
18227433 F.R.Salsbury, S.T.Knutson, L.B.Poole, and J.S.Fetrow (2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
  Protein Sci, 17, 299-312.  
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.  
18709443 J.R.Cort, T.A.Ramelot, D.Murray, T.B.Acton, L.C.Ma, R.Xiao, G.T.Montelione, and M.A.Kennedy (2008).
Structure of an acetyl-CoA binding protein from Staphylococcus aureus representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins.
  J Struct Funct Genomics, 9, 7.
PDB codes: 1r57 2h5m
18845255 L.Wang, Y.Tang, P.A.Cole, and R.Marmorstein (2008).
Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and function.
  Curr Opin Struct Biol, 18, 741-747.  
18245364 P.V.Decker, D.Y.Yu, M.Iizuka, Q.Qiu, and M.M.Smith (2008).
Catalytic-site mutations in the MYST family histone Acetyltransferase Esa1.
  Genetics, 178, 1209-1220.  
18631159 T.Kawahara, T.N.Siegel, A.K.Ingram, S.Alsford, G.A.Cross, and D.Horn (2008).
Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes.
  Mol Microbiol, 69, 1054-1068.  
18568037 Y.Tang, M.A.Holbert, H.Wurtele, K.Meeth, W.Rocha, M.Gharib, E.Jiang, P.Thibault, A.Verrault, P.A.Cole, and R.Marmorstein (2008).
Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP.
  Nat Struct Mol Biol, 15, 738-745.
PDB codes: 3d35 3qm0
17656314 A.Misra, S.K.Sharma, N.Surolia, and A.Surolia (2007).
Self-acylation properties of type II fatty acid biosynthesis acyl carrier protein.
  Chem Biol, 14, 775-783.  
17223684 C.E.Berndsen, B.N.Albaugh, S.Tan, and J.M.Denu (2007).
Catalytic mechanism of a MYST family histone acetyltransferase.
  Biochemistry, 46, 623-629.  
17274630 C.E.Berndsen, W.Selleck, S.J.McBryant, J.C.Hansen, S.Tan, and J.M.Denu (2007).
Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex.
  Biochemistry, 46, 2091-2099.  
17642514 E.Hidber, E.R.Brownie, K.Hayakawa, and M.E.Fraser (2007).
Participation of Cys123alpha of Escherichia coli succinyl-CoA synthetase in catalysis.
  Acta Crystallogr D Biol Crystallogr, 63, 876-884.
PDB codes: 2nu6 2nu7 2nu8 2nu9 2nua
17925393 M.A.Holbert, T.Sikorski, J.Carten, D.Snowflack, S.Hodawadekar, and R.Marmorstein (2007).
The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting.
  J Biol Chem, 282, 36603-36613.
PDB code: 2rc4
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
16503658 J.C.Errey, and J.S.Blanchard (2006).
Functional annotation and kinetic characterization of PhnO from Salmonella enterica.
  Biochemistry, 45, 3033-3039.  
17070031 J.F.Couture, and R.C.Trievel (2006).
Histone-modifying enzymes: encrypting an enigmatic epigenetic code.
  Curr Opin Struct Biol, 16, 753-760.  
17128971 R.C.Tyler, E.Bitto, C.E.Berndsen, C.A.Bingman, S.Singh, M.S.Lee, G.E.Wesenberg, J.M.Denu, G.N.Phillips, and J.L.Markley (2006).
Structure of Arabidopsis thaliana At1g77540 protein, a minimal acetyltransferase from the COG2388 family.
  Biochemistry, 45, 14325-14336.
PDB codes: 1xmt 2evn 2gdb 2il4
16698308 V.Sapountzi, I.R.Logan, and C.N.Robson (2006).
Cellular functions of TIP60.
  Int J Biochem Cell Biol, 38, 1496-1509.  
16339723 A.T.Smith, S.D.Tucker-Samaras, A.H.Fairlamb, and W.J.Sullivan (2005).
MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii.
  Eukaryot Cell, 4, 2057-2065.  
15838030 J.C.Errey, and J.S.Blanchard (2005).
Functional characterization of a novel ArgA from Mycobacterium tuberculosis.
  J Bacteriol, 187, 3039-3044.  
16024812 M.Taipale, S.Rea, K.Richter, A.Vilar, P.Lichter, A.Imhof, and A.Akhtar (2005).
hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells.
  Mol Cell Biol, 25, 6798-6810.  
15817456 M.W.Vetting, Carvalho, S.L.Roderick, and J.S.Blanchard (2005).
A novel dimeric structure of the RimL Nalpha-acetyltransferase from Salmonella typhimurium.
  J Biol Chem, 280, 22108-22114.
PDB codes: 1s7f 1s7k 1s7l 1s7n
15485860 C.Toleman, A.J.Paterson, T.R.Whisenhunt, and J.E.Kudlow (2004).
Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities.
  J Biol Chem, 279, 53665-53673.  
15375647 G.Y.Yow, T.Uo, T.Yoshimura, and N.Esaki (2004).
D-amino acid N-acetyltransferase of Saccharomyces cerevisiae: a close homologue of histone acetyltransferase Hpa2p acting exclusively on free D-amino acids.
  Arch Microbiol, 182, 396-403.  
14960713 X.J.Yang (2004).
The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases.
  Nucleic Acids Res, 32, 959-976.  
12930994 M.W.Vetting, S.L.Roderick, M.Yu, and J.S.Blanchard (2003).
Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases.
  Protein Sci, 12, 1954-1959.
PDB codes: 1ozp 1p0h
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.