PDBsum entry 1ygh

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Gene regulation PDB id
Protein chains
164 a.a. *
GOL ×2
Waters ×216
* Residue conservation analysis
PDB id:
Name: Gene regulation
Title: Hat domain of gcn5 from saccharomyces cerevisiae
Structure: Protein (transcriptional activator gcn5). Chain: a, b. Fragment: histone acetyltransferase domain. Synonym: ada4. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Cellular_location: nuclear. Gene: gcn5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.90Å     R-factor:   0.195     R-free:   0.236
Authors: R.C.Trievel,J.R.Rojas,D.E.Sterner,R.Venkataramani,L.Wang,J.Z C.D.Allis,S.L.Berger,R.Marmorstein
Key ref:
R.C.Trievel et al. (1999). Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator. Proc Natl Acad Sci U S A, 96, 8931-8936. PubMed id: 10430873 DOI: 10.1073/pnas.96.16.8931
27-May-99     Release date:   02-Aug-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q03330  (GCN5_YEAST) -  Histone acetyltransferase GCN5
439 a.a.
164 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Histone acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [histone] = CoA + acetyl-[histone]
+ [histone]
= CoA
+ acetyl-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     N-acetyltransferase activity     1 term  


    Added reference    
DOI no: 10.1073/pnas.96.16.8931 Proc Natl Acad Sci U S A 96:8931-8936 (1999)
PubMed id: 10430873  
Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator.
R.C.Trievel, J.R.Rojas, D.E.Sterner, R.N.Venkataramani, L.Wang, J.Zhou, C.D.Allis, S.L.Berger, R.Marmorstein.
The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Here, we present the high resolution crystal structure of the HAT domain of yGCN5 and probe the functional importance of a conserved glutamate residue. The structure reveals a central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase. A pronounced cleft lying above this core, and flanked by N- and C-terminal regions that show no sequence conservation within N-acetyltransferase enzymes, is implicated by cross-species conservation and mutagenesis studies to be a site for histone substrate binding and catalysis. Located at the bottom of this cleft is a conserved glutamate residue (E173) that is in position to play an important catalytic role in histone acetylation. Functional analysis of an E173Q mutant yGCN5 protein implicates glutamate 173 to function as a general base for catalysis. Together, a correlation of the yGCN5 structure with functionally debilitating yGCN5 mutations provides a paradigm for understanding the structure/function relationships of the growing number of transcriptional regulators that function as histone acetyltransferase enzymes.
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of yGCN5 and related enzymes. (a) Structure of the yGCN5 HAT domain. The four subdomains of the protein are color-coded; the structurally conserved subdomain that makes up the core (motifs A and D) is colored blue, motif B is colored aqua, and the N-terminal and C-terminal flanking regions are colored red and green, respectively. (b) Structure of residues 130-320 (C terminus) of HAT1 with the same orientation and color coding as in a. The AcCoA cofactor is shown in magenta. (c) Structure of SmAAT with the same orientation and color coding as in a. The CoA cofactor is shown in magenta. (d) Structure of residues 80-260 (N terminus) of NMT with the same orientation and color coding as in a.
Figure 3.
Fig. 3. Implications of the yGCN5 structure for HAT function. (a) Strictly conserved residues within the GCN5 subfamily of acetyltransferases (Fig. 2) that are buried and thus play a role in protein stability are indicated as red balls, and strictly conserved and solvent exposed yGCN5 residues (Fig. 2) (implicated for histone substrate or CoA cofactor binding or catalysis) are shown as green side-chains. AcCoA from the HAT1 structure is placed in the cofactor binding site for reference by superposing the HAT1 core domain. Secondary structural elements are indicated for reference. (b) Mutations in yGCN5 that decrease HAT activity are mapped onto a schematic representation of the yGCN5 HAT domain. Triple mutations are shown as green side chains, and single mutations are shown as red side chains. (c) Electrostatic surface of the yGCN5 HAT domain. Red indicates acidic regions, and blue indicates basic regions. A backbone trace of the protein is superimposed in green. (d) SigmaA-weighted |F[o]| |F[c]| omit map around the region of residue Glu173, which is implicated to function as a catalytic base for substrate catalysis. The map was generated by omitting residues within an 8-Å radius of Glu 173 followed by simulated annealing dynamics refinement at a temperature of 1,000 K. The map is contoured at 1.8 sigma. The green sphere indicates a water molecule.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20531298 E.H.Jeninga, K.Schoonjans, and J.Auwerx (2010).
Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility.
  Oncogene, 29, 4617-4624.  
19889644 K.Oda, Y.Matoba, M.Noda, T.Kumagai, and M.Sugiyama (2010).
Catalytic mechanism of bleomycin N-acetyltransferase proposed on the basis of its crystal structure.
  J Biol Chem, 285, 1446-1456.
PDB codes: 2zw4 2zw5 2zw6 2zw7
20048049 S.K.Lee, A.G.Fletcher, L.Zhang, X.Chen, J.A.Fischbeck, and L.A.Stargell (2010).
Activation of a poised RNAPII-dependent promoter requires both SAGA and mediator.
  Genetics, 184, 659-672.  
19841091 Y.Liu, X.Xu, and M.H.Kuo (2010).
Snf1p regulates Gcn5p transcriptional activity by antagonizing Spt3p.
  Genetics, 184, 91.  
19683498 B.S.Atanassov, Y.A.Evrard, A.S.Multani, Z.Zhang, L.Tora, D.Devys, S.Chang, and S.Y.Dent (2009).
Gcn5 and SAGA regulate shelterin protein turnover and telomere maintenance.
  Mol Cell, 35, 352-364.  
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.  
19744929 R.Evjenth, K.Hole, O.A.Karlsen, M.Ziegler, T.Arnesen, and J.R.Lillehaug (2009).
Human Naa50p (Nat5/San) displays both protein N alpha- and N epsilon-acetyltransferase activity.
  J Biol Chem, 284, 31122-31129.  
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.  
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.  
18719104 P.Stavropoulos, V.Nagy, G.Blobel, and A.Hoelz (2008).
Molecular basis for the autoregulation of the protein acetyl transferase Rtt109.
  Proc Natl Acad Sci U S A, 105, 12236-12241.
PDB code: 3cz7
18373682 T.Kotani, and H.Takagi (2008).
Identification of amino acid residues essential for the yeast N-acetyltransferase Mpr1 activity by site-directed mutagenesis.
  FEMS Yeast Res, 8, 607-614.  
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
17410582 A.Schuetz, G.Bernstein, A.Dong, T.Antoshenko, H.Wu, P.Loppnau, A.Bochkarev, and A.N.Plotnikov (2007).
Crystal structure of a binary complex between human GCN5 histone acetyltransferase domain and acetyl coenzyme A.
  Proteins, 68, 403-407.
PDB code: 1z4r
17380162 K.K.Lee, and J.L.Workman (2007).
Histone acetyltransferase complexes: one size doesn't fit all.
  Nat Rev Mol Cell Biol, 8, 284-295.  
17694075 M.R.Parthun (2007).
Hat1: the emerging cellular roles of a type B histone acetyltransferase.
  Oncogene, 26, 5319-5328.  
17694092 S.C.Hodawadekar, and R.Marmorstein (2007).
Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design.
  Oncogene, 26, 5528-5540.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
16705163 D.Mitra, E.J.Parnell, J.W.Landon, Y.Yu, and D.J.Stillman (2006).
SWI/SNF binding to the HO promoter requires histone acetylation and stimulates TATA-binding protein recruitment.
  Mol Cell Biol, 26, 4095-4110.  
16543222 J.E.Babiarz, J.E.Halley, and J.Rine (2006).
Telomeric heterochromatin boundaries require NuA4-dependent acetylation of histone variant H2A.Z in Saccharomyces cerevisiae.
  Genes Dev, 20, 700-710.  
16400169 M.M.Bhatti, M.Livingston, N.Mullapudi, and W.J.Sullivan (2006).
Pair of unusual GCN5 histone acetyltransferases and ADA2 homologues in the protozoan parasite Toxoplasma gondii.
  Eukaryot Cell, 5, 62-76.  
16855251 M.N.Hung, E.Rangarajan, C.Munger, G.Nadeau, T.Sulea, and A.Matte (2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
  J Bacteriol, 188, 5606-5617.
PDB codes: 2fs5 2ft0
15657441 K.Ingvarsdottir, N.J.Krogan, N.C.Emre, A.Wyce, N.J.Thompson, A.Emili, T.R.Hughes, J.F.Greenblatt, and S.L.Berger (2005).
H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex.
  Mol Cell Biol, 25, 1162-1172.  
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.  
15870300 T.L.Hilton, Y.Li, E.L.Dunphy, and E.H.Wang (2005).
TAF1 histone acetyltransferase activity in Sp1 activation of the cyclin D1 promoter.
  Mol Cell Biol, 25, 4321-4332.  
16287868 Y.Liu, X.Xu, S.Singh-Rodriguez, Y.Zhao, and M.H.Kuo (2005).
Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression.
  Mol Cell Biol, 25, 10566-10579.  
15468321 J.S.Brunzelle, R.Wu, S.V.Korolev, F.R.Collart, A.Joachimiak, and W.F.Anderson (2004).
Crystal structure of Bacillus subtilis YdaF protein: a putative ribosomal N-acetyltransferase.
  Proteins, 57, 850-853.
PDB code: 1nsl
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
15075257 Q.Fan, L.An, and L.Cui (2004).
Plasmodium falciparum histone acetyltransferase, a yeast GCN5 homologue involved in chromatin remodeling.
  Eukaryot Cell, 3, 264-276.  
14661947 A.N.Poux, and R.Marmorstein (2003).
Molecular basis for Gcn5/PCAF histone acetyltransferase selectivity for histone and nonhistone substrates.
  Biochemistry, 42, 14366-14374.
PDB code: 1q2d
14635137 B.Taneja, S.Maar, L.Shuvalova, F.Collart, W.Anderson, and A.Mondragón (2003).
Structure of the bacillus subtilis YYCN protein: a putative N-acetyltransferase.
  Proteins, 53, 950-952.
PDB code: 1ufh
12592013 D.L.Burk, N.Ghuman, L.E.Wybenga-Groot, and A.M.Berghuis (2003).
X-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members.
  Protein Sci, 12, 426-437.
PDB code: 1n71
12612066 Y.Yu, P.Eriksson, L.T.Bhoite, and D.J.Stillman (2003).
Regulation of TATA-binding protein binding by the SAGA complex and the Nhp6 high-mobility group protein.
  Mol Cell Biol, 23, 1910-1921.  
12024017 A.R.Ricci, J.Genereaux, and C.J.Brandl (2002).
Components of the SAGA histone acetyltransferase complex are required for repressed transcription of ARG1 in rich medium.
  Mol Cell Biol, 22, 4033-4042.  
12186975 D.E.Sterner, R.Belotserkovskaya, and S.L.Berger (2002).
SALSA, a variant of yeast SAGA, contains truncated Spt7, which correlates with activated transcription.
  Proc Natl Acad Sci U S A, 99, 11622-11627.  
12161746 M.W.Vetting, S.S.Hegde, F.Javid-Majd, J.S.Blanchard, and S.L.Roderick (2002).
Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates.
  Nat Struct Biol, 9, 653-658.
PDB codes: 1m44 1m4d 1m4g 1m4i
12368900 Y.Yan, S.Harper, D.W.Speicher, and R.Marmorstein (2002).
The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate.
  Nat Struct Biol, 9, 862-869.
PDB codes: 1mj9 1mja 1mjb
11709299 A.Shmara, N.Weinsetel, K.J.Dery, R.Chavideh, and M.E.Tolmasky (2001).
Systematic analysis of a conserved region of the aminoglycoside 6'-N-acetyltransferase type Ib.
  Antimicrob Agents Chemother, 45, 3287-3292.  
11691934 L.Bordoli, S.Hüsser, U.Lüthi, M.Netsch, H.Osmani, and R.Eckner (2001).
Functional analysis of the p300 acetyltransferase domain: the PHD finger of p300 but not of CBP is dispensable for enzymatic activity.
  Nucleic Acids Res, 29, 4462-4471.  
11250138 R.Marmorstein, and S.Y.Roth (2001).
Histone acetyltransferases: function, structure, and catalysis.
  Curr Opin Genet Dev, 11, 155-161.  
11395403 S.Y.Roth, J.M.Denu, and C.D.Allis (2001).
Histone acetyltransferases.
  Annu Rev Biochem, 70, 81.  
10839822 D.E.Sterner, and S.L.Berger (2000).
Acetylation of histones and transcription-related factors.
  Microbiol Mol Biol Rev, 64, 435-459.  
11080160 D.J.Owen, P.Ornaghi, J.C.Yang, N.Lowe, P.R.Evans, P.Ballario, D.Neuhaus, P.Filetici, and A.A.Travers (2000).
The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase gcn5p.
  EMBO J, 19, 6141-6149.
PDB code: 1e6i
10940244 F.Dyda, D.C.Klein, and A.B.Hickman (2000).
GCN5-related N-acetyltransferases: a structural overview.
  Annu Rev Biophys Biomol Struct, 29, 81.  
11009610 K.G.Tanner, M.R.Langer, and J.M.Denu (2000).
Kinetic mechanism of human histone acetyltransferase P/CAF.
  Biochemistry, 39, 11961-11969.  
11114158 Q.Zhang, H.Yao, N.Vo, and R.H.Goodman (2000).
Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP.
  Proc Natl Acad Sci U S A, 97, 14323-14328.  
11114889 S.J.Nowak, and V.G.Corces (2000).
Phosphorylation of histone H3 correlates with transcriptionally active loci.
  Genes Dev, 14, 3003-3013.  
11123906 T.A.Farazi, J.K.Manchester, and J.I.Gordon (2000).
Transient-state kinetic analysis of Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase reveals that a step after chemical transformation is rate limiting.
  Biochemistry, 39, 15807-15816.  
10911986 W.S.Lo, R.C.Trievel, J.R.Rojas, L.Duggan, J.Y.Hsu, C.D.Allis, R.Marmorstein, and S.L.Berger (2000).
Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.
  Mol Cell, 5, 917-926.  
10949041 Y.Lorch, J.Beve, C.M.Gustafsson, L.C.Myers, and R.D.Kornberg (2000).
Mediator-nucleosome interaction.
  Mol Cell, 6, 197-201.  
11106757 Y.Yan, N.A.Barlev, R.H.Haley, S.L.Berger, and R.Marmorstein (2000).
Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
  Mol Cell, 6, 1195-1205.
PDB code: 1fy7
10629113 J.R.Davie, and V.A.Spencer (1999).
Control of histone modifications.
  J Cell Biochem, (), 141-148.  
10430845 R.Sternglanz, and H.Schindelin (1999).
Structure and mechanism of action of the histone acetyltransferase Gcn5 and similarity to other N-acetyltransferases.
  Proc Natl Acad Sci U S A, 96, 8807-8808.  
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.