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protein ligands metals links
Hydrolase PDB id
1it6
Jmol
Contents
Protein chains
293 a.a. *
Ligands
CYU ×2
Metals
_MN ×4
Waters ×96
* Residue conservation analysis
PDB id:
1it6
Name: Hydrolase
Title: Crystal structure of the complex between calyculin a and the catalytic subunit of protein phosphatase 1
Structure: Serine/threonine protein phosphatase 1 gamma (pp1-gamma) catalytic subunit. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.182     R-free:   0.218
Authors: A.Kita,S.Matsunaga,A.Takai,H.Kataiwa,T.Wakimoto,N.Fusetani, M.Isobe,K.Miki
Key ref:
A.Kita et al. (2002). Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1. Structure, 10, 715-724. PubMed id: 12015153 DOI: 10.1016/S0969-2126(02)00764-5
Date:
09-Jan-02     Release date:   22-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P36873  (PP1G_HUMAN) -  Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
Seq:
Struc: 		323 a.a.
293 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.16  - Phosphoprotein phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A phosphoprotein + H2O = a protein + phosphate
phosphoprotein
 + H(2)O
 = protein
 + phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   10 terms 
  Biological process     cell cycle   4 terms 
  Biochemical function     protein binding     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(02)00764-5 Structure 10:715-724 (2002)
PubMed id: 12015153  
 
 
Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1.
A.Kita, S.Matsunaga, A.Takai, H.Kataiwa, T.Wakimoto, N.Fusetani, M.Isobe, K.Miki.
 
  ABSTRACT  
 
The crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1 gamma, in complex with a marine toxin, calyculin A, was determined at 2.0 A resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseudocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1 gamma, which is consistent with findings from the studies of dose-inhibition analysis.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The Overall Structure of PP1g-Calyculin A ComplexSchematic diagram of the three-dimensional structure of PP1g, drawn by the program MOLSCRIPT [44], and rendered by RASTER3D [45]. The calyculin A molecule is shown in ball and stick representation. Colors are employed to identify the helices and strands. Metal ions, gold circles; b12-b13 loop, red.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 715-724) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21288162 S.R.Pereira, V.T.Vasconcelos, and A.Antunes (2011).
The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins.
  Crit Rev Toxicol, 41, 83.  
20161975 A.E.Fagerholm, D.Habrant, and A.M.Koskinen (2010).
Calyculins and related marine natural products as serine-threonine protein phosphatase PP1 and PP2A inhibitors and total syntheses of calyculin A, B, and C.
  Mar Drugs, 8, 122-172.  
20683542 D.Habrant, and A.M.Koskinen (2010).
Towards the total synthesis of calyculin C: preparation of the C(9)-C(25) spiroketal-dipropionate unit.
  Org Biomol Chem, 8, 4364-4373.  
20305656 M.J.Ragusa, B.Dancheck, D.A.Critton, A.C.Nairn, R.Page, and W.Peti (2010).
Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.
  Nat Struct Mol Biol, 17, 459-464.
PDB codes: 3egg 3egh 3hvq
18992256 M.S.Kelker, R.Page, and W.Peti (2009).
Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors.
  J Mol Biol, 385, 11-21.
PDB codes: 3e7a 3e7b
18954090 B.Dancheck, A.C.Nairn, and W.Peti (2008).
Detailed structural characterization of unbound protein phosphatase 1 inhibitors.
  Biochemistry, 47, 12346-12356.  
19330070 J.Y.Cho, and J.Park (2008).
Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade.
  Int J Mol Sci, 9, 2217-2230.  
18708355 W.Li, J.Ju, S.R.Rajski, H.Osada, and B.Shen (2008).
Characterization of the Tautomycin Biosynthetic Gene Cluster from Streptomyces spiroverticillatus Unveiling New Insights into Dialkylmaleic Anhydride and Polyketide Biosynthesis.
  J Biol Chem, 283, 28607-28617.  
17939754 L.Ni, M.S.Swingle, A.C.Bourgeois, and R.E.Honkanen (2007).
High yield expression of serine/threonine protein phosphatase type 5, and a fluorescent assay suitable for use in the detection of catalytic inhibitors.
  Assay Drug Dev Technol, 5, 645-653.  
17441173 M.Isobe, M.Kurono, K.Tsuboi, and A.Takai (2007).
Synthesis of [18,19,21,22-(13)C4]-labeled tautomycin as an NMR probe of protein phosphatase inhibitor.
  Chem Asian J, 2, 377-385.  
17055435 Y.Xing, Y.Xu, Y.Chen, P.D.Jeffrey, Y.Chao, Z.Lin, Z.Li, S.Strack, J.B.Stock, and Y.Shi (2006).
Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins.
  Cell, 127, 341-353.
PDB codes: 2ie3 2ie4
15703180 J.A.Gibbons, D.C.Weiser, and S.Shenolikar (2005).
Importance of a surface hydrophobic pocket on protein phosphatase-1 catalytic subunit in recognizing cellular regulators.
  J Biol Chem, 280, 15903-15911.  
15577939 J.Yang, S.M.Roe, M.J.Cliff, M.A.Williams, J.E.Ladbury, P.T.Cohen, and D.Barford (2005).
Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.
  EMBO J, 24, 1.
PDB code: 1wao
15981249 O.Schueler-Furman, C.Wang, and D.Baker (2005).
Progress in protein-protein docking: atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility.
  Proteins, 60, 187-194.  
15504744 I.T.Makagiansar, S.Williams, K.Dahlin-Huppe, J.Fukushi, T.Mustelin, and W.B.Stallcup (2004).
Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized membrane distribution and cell motility.
  J Biol Chem, 279, 55262-55270.  
15280359 J.T.Maynes, K.R.Perreault, M.M.Cherney, H.A.Luu, M.N.James, and C.F.Holmes (2004).
Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding.
  J Biol Chem, 279, 43198-43206.
PDB code: 1u32
15155720 M.R.Swingle, R.E.Honkanen, and E.M.Ciszak (2004).
Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5.
  J Biol Chem, 279, 33992-33999.
PDB code: 1s95
15164081 M.Terrak, F.Kerff, K.Langsetmo, T.Tao, and R.Dominguez (2004).
Structural basis of protein phosphatase 1 regulation.
  Nature, 429, 780-784.
PDB code: 1s70
15252037 T.D.Prickett, and D.L.Brautigan (2004).
Overlapping binding sites in protein phosphatase 2A for association with regulatory A and alpha-4 (mTap42) subunits.
  J Biol Chem, 279, 38912-38920.  
12694636 J.Y.Jeong, J.Johns, C.Sinclair, J.M.Park, and S.Rossie (2003).
Characterization of Saccharomyces cerevisiae protein Ser/Thr phosphatase T1 and comparison to its mammalian homolog PP5.
  BMC Cell Biol, 4, 3.  
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.