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PDBsum entry 1q1a
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protein ligands metals links
Gene regulation PDB id
1q1a

 

 

 

 

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Contents
Protein chain
285 a.a. *
Ligands
LYS-GLY-GLY-ALA-
ALY-ARG-HIS-ARG-
LYS-ILE
OAD
Metals
_ZN
Waters ×303
* Residue conservation analysis
PDB id:
1q1a
Name: Gene regulation
Title: Structure of the yeast hst2 protein deacetylase in ternary complex with 2'-o-acetyl adp ribose and histone peptide
Structure: Hst2 protein. Chain: a. Fragment: c-terminla deletion of hst2. Synonym: homologous to sir2 protein 2. Engineered: yes. Histone h4. Chain: b. Fragment: residues 12-21. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chemically synthesized
Biol. unit: Dimer (from PQS)
Resolution:
1.50Å     R-factor:   0.183     R-free:   0.210
Authors: K.Zhao,X.Chai,R.Marmorstein
Key ref:
K.Zhao et al. (2003). Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide. Structure, 11, 1403-1411. PubMed id: 14604530 DOI: 10.1016/j.str.2003.09.016
Date:
18-Jul-03     Release date:   18-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P53686  (HST2_YEAST) -  NAD-dependent protein deacetylase HST2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		357 a.a.
285 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.286  - protein acetyllysine N-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N6-acetyl-L-lysyl-[protein] + NAD+ + H2O = 2''-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]
N(6)-acetyl-L-lysyl-[protein]
 + NAD(+)
 + H2O
Bound ligand (Het Group name = OAD)
matches with 72.92% similarity 		= 2''-O-acetyl-ADP-D-ribose
 + nicotinamide
 + L-lysyl-[protein]
Bound ligand (Het Group name = ALY)
matches with 61.54% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/j.str.2003.09.016 Structure 11:1403-1411 (2003)
PubMed id: 14604530  
 
 
Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide.
K.Zhao, X.Chai, R.Marmorstein.
 
  ABSTRACT  
 
Sir2 proteins are NAD(+)-dependant protein deactylases that have been implicated in playing roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. To define the mechanism of Sir2 activity, we report the 1.5 A crystal structure of the yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP ribose and an acetylated histone H4 peptide. The structure captures both ligands meeting within an enclosed tunnel between the small and large domains of the catalytic protein core and permits the assignment of a detailed catalytic mechanism for the Sir2 proteins that is consistent with solution and enzymatic studies. Comparison of the ternary complex with the yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also reveals that NAD(+) binding accompanies intramolecular loop rearrangement for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine peptide binding induces a trimer-monomer protein transition involving nonconserved Sir2 residues.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. The yHst2-Histone H4 Interface(A) Stereo view of yHst2-histone H4 interactions within the ternary complex. Hydrogen bonds are indicated with a dashed line. Residues that mediate van der Waals interactions are also shown.(B) Summary of yHst2-histone H4 interactions. Hydrogen bonds are indicated with a dashed line, and van der Waals interactions are indicated with a half-moon symbol. For clarity, histone H4 side chains that do no participate in direct protein-peptide interactions are not shown. The residues highlighted in cyan and red highlight interactions with acetly-lysine peptide substrate that are conserved and nonconserved, respectively, with the protein-peptide interactions observed in the Af2-Sir2/p53 peptide structure.(C) The p53 peptide (purple) from the Af2-Sir2/p53 peptide structure and the "pseudosubstrate" from the nascent yHst2 structure (yellow) are overlayed with the histone H4 peptide (green) onto a surface representation of yHst2 from the ternary complex. Protein residues that make conserved interactions between the three substrates are indicated in blue, and protein residues that mediate variable interactions are indicated in red.(D) Backbone overlay of yHst2/NAD^+ (gray) and nascent yHst2 (cyan) homotrimers with the yHst2/2'-O-acetyl ADP ribose/histone H4 monomer (red). The ADP-ribose is highlighted in yellow, the histone H4 peptide is highlighted in green, and the C-terminal domain of nascent yHst2 is highlighted in purple.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1403-1411) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21080423 P.Bheda, J.T.Wang, J.C.Escalante-Semerena, and C.Wolberger (2011).
Structure of Sir2Tm bound to a propionylated peptide.
  Protein Sci, 20, 131-139.
PDB code: 3pdh
19404761 S.Kaur, A.V.Shivange, and N.Roy (2010).
Structural analysis of trypanosomal sirtuin: an insight for selective drug design.
  Mol Divers, 14, 169-178.  
19355989 D.Wang (2009).
Computational studies on the histone deacetylases and the design of selective histone deacetylase inhibitors.
  Curr Top Med Chem, 9, 241-256.  
19136592 J.G.Gardner, and J.C.Escalante-Semerena (2009).
In Bacillus subtilis, the sirtuin protein deacetylase, encoded by the srtN gene (formerly yhdZ), and functions encoded by the acuABC genes control the activity of acetyl coenzyme A synthetase.
  J Bacteriol, 191, 1749-1755.  
19535340 L.Jin, W.Wei, Y.Jiang, H.Peng, J.Cai, C.Mao, H.Dai, W.Choy, J.E.Bemis, M.R.Jirousek, J.C.Milne, C.H.Westphal, and R.B.Perni (2009).
Crystal structures of human SIRT3 displaying substrate-induced conformational changes.
  J Biol Chem, 284, 24394-24405.
PDB codes: 3glr 3gls 3glt 3glu
19688789 Z.A.Gurard-Levin, J.Kim, and M.Mrksich (2009).
Combining mass spectrometry and peptide arrays to profile the specificities of histone deacetylases.
  Chembiochem, 10, 2159-2161.  
18845844 C.L.Wang, J.Landry, and R.Sternglanz (2008).
A yeast sir2 mutant temperature sensitive for silencing.
  Genetics, 180, 1955-1962.  
18729382 J.B.French, Y.Cen, and A.A.Sauve (2008).
Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase.
  Biochemistry, 47, 10227-10239.  
19049465 P.Hu, S.Wang, and Y.Zhang (2008).
Highly dissociative and concerted mechanism for the nicotinamide cleavage reaction in Sir2Tm enzyme suggested by ab initio QM/MM molecular dynamics simulations.
  J Am Chem Soc, 130, 16721-16728.  
18812159 S.Lee, L.Tong, and J.M.Denu (2008).
Quantification of endogenous sirtuin metabolite O-acetyl-ADP-ribose.
  Anal Biochem, 383, 174-179.  
18786399 W.F.Hawse, K.G.Hoff, D.G.Fatkins, A.Daines, O.V.Zubkova, V.L.Schramm, W.Zheng, and C.Wolberger (2008).
Structural insights into intermediate steps in the Sir2 deacetylation reaction.
  Structure, 16, 1368-1377.
PDB codes: 3d4b 3d81
18470998 Z.A.Gurard-Levin, and M.Mrksich (2008).
The activity of HDAC8 depends on local and distal sequences of its peptide substrates.
  Biochemistry, 47, 6242-6250.  
17355872 A.Schuetz, J.Min, T.Antoshenko, C.L.Wang, A.Allali-Hassani, A.Dong, P.Loppnau, M.Vedadi, A.Bochkarev, R.Sternglanz, and A.N.Plotnikov (2007).
Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin.
  Structure, 15, 377-389.
PDB code: 2nyr
17289592 B.D.Sanders, K.Zhao, J.T.Slama, and R.Marmorstein (2007).
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes.
  Mol Cell, 25, 463-472.
PDB codes: 2od2 2od7 2od9 2qqf 2qqg
17827348 C.J.Merrick, and M.T.Duraisingh (2007).
Plasmodium falciparum Sir2: an unusual sirtuin with dual histone deacetylase and ADP-ribosyltransferase activity.
  Eukaryot Cell, 6, 2081-2091.  
18019526 H.Lin (2007).
Nicotinamide adenine dinucleotide: beyond a redox coenzyme.
  Org Biomol Chem, 5, 2541-2554.  
17156081 H.Yang, J.A.Baur, A.Chen, C.Miller, J.K.Adams, A.Kisielewski, K.T.Howitz, R.E.Zipkin, and D.A.Sinclair (2007).
Design and synthesis of compounds that extend yeast replicative lifespan.
  Aging Cell, 6, 35-43.  
17242192 J.Mead, R.McCord, L.Youngster, M.Sharma, M.R.Gartenberg, and A.K.Vershon (2007).
Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases.
  Mol Cell Biol, 27, 2466-2475.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
16756498 A.A.Sauve, C.Wolberger, V.L.Schramm, and J.D.Boeke (2006).
The biochemistry of sirtuins.
  Annu Rev Biochem, 75, 435-465.  
17018288 A.G.Ladurner (2006).
Rheostat control of gene expression by metabolites.
  Mol Cell, 24, 1.  
16388584 A.L.Garske, and J.M.Denu (2006).
SIRT1 top 40 hits: use of one-bead, one-compound acetyl-peptide libraries and quantum dots to probe deacetylase specificity.
  Biochemistry, 45, 94.  
16520376 A.N.Khan, and P.N.Lewis (2006).
Use of substrate analogs and mutagenesis to study substrate binding and catalysis in the Sir2 family of NAD-dependent protein deacetylases.
  J Biol Chem, 281, 11702-11711.  
16388603 B.C.Smith, and J.M.Denu (2006).
Sir2 protein deacetylases: evidence for chemical intermediates and functions of a conserved histidine.
  Biochemistry, 45, 272-282.  
17035629 B.Yang, and A.L.Kirchmaier (2006).
Bypassing the catalytic activity of SIR2 for SIR protein spreading in Saccharomyces cerevisiae.
  Mol Biol Cell, 17, 5287-5297.  
16717101 D.A.King, B.E.Hall, M.A.Iwamoto, K.Z.Win, J.F.Chang, and T.Ellenberger (2006).
Domain structure and protein interactions of the silent information regulator Sir3 revealed by screening a nested deletion library of protein fragments.
  J Biol Chem, 281, 20107-20119.  
17048004 D.Sereno, B.Vergnes, F.Mathieu-Daude, A.Cordeiro da Silva, and A.Ouaissi (2006).
Looking for putative functions of the Leishmania cytosolic SIR2 deacetylase.
  Parasitol Res, 100, 1-9.  
16905097 K.G.Hoff, J.L.Avalos, K.Sens, and C.Wolberger (2006).
Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide.
  Structure, 14, 1231-1240.
PDB codes: 2h4f 2h4h 2h4j 2h59
16131486 A.N.Khan, and P.N.Lewis (2005).
Unstructured conformations are a substrate requirement for the Sir2 family of NAD-dependent protein deacetylases.
  J Biol Chem, 280, 36073-36078.  
15642260 E.A.Sickmier, D.Brekasis, S.Paranawithana, J.B.Bonanno, M.S.Paget, S.K.Burley, and C.L.Kielkopf (2005).
X-ray structure of a Rex-family repressor/NADH complex insights into the mechanism of redox sensing.
  Structure, 13, 43-54.
PDB code: 1xcb
15780941 J.L.Avalos, K.M.Bever, and C.Wolberger (2005).
Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme.
  Mol Cell, 17, 855-868.
PDB codes: 1yc2 1yc5
16122969 J.M.Denu (2005).
The Sir 2 family of protein deacetylases.
  Curr Opin Chem Biol, 9, 431-440.  
15999106 K.G.Hoff, and C.Wolberger (2005).
Getting a grip on O-acetyl-ADP-ribose.
  Nat Struct Mol Biol, 12, 560-561.
PDB code: 1zr3
15611301 R.Sawaya, B.Schwer, and S.Shuman (2005).
Structure-function analysis of the yeast NAD+-dependent tRNA 2'-phosphotransferase Tpt1.
  RNA, 11, 107-113.  
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 code is shown on the right.

 

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