PDBsum entry 2bdx

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Hydrolase/hydrolase inhibitor PDB id
Protein chain
293 a.a. *
_MN ×2
Waters ×35
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: X-ray crystal structure of dihydromicrocystin-la bound to pr phosphatase-1
Structure: Serine/threonine protein phosphatase pp1-gamma ca subunit. Chain: a. Synonym: pp-1g, protein phosphatase 1c catalytic subunit. Engineered: yes. Dihydromicrocystin-la. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp1cc. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
2.30Å     R-factor:   0.214     R-free:   0.250
Authors: J.T.Maynes,H.A.Luu,M.M.Cherney,R.J.Andersen,D.Williams,C.F.H M.N.James
Key ref:
J.T.Maynes et al. (2006). Crystal structures of protein phosphatase-1 bound to motuporin and dihydromicrocystin-LA: elucidation of the mechanism of enzyme inhibition by cyanobacterial toxins. J Mol Biol, 356, 111-120. PubMed id: 16343532 DOI: 10.1016/j.jmb.2005.11.019
21-Oct-05     Release date:   17-Jan-06    
Go to PROCHECK summary

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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     PTW/PP1 phosphatase complex   17 terms 
  Biological process     small molecule metabolic process   14 terms 
  Biochemical function     protein binding     9 terms  


DOI no: 10.1016/j.jmb.2005.11.019 J Mol Biol 356:111-120 (2006)
PubMed id: 16343532  
Crystal structures of protein phosphatase-1 bound to motuporin and dihydromicrocystin-LA: elucidation of the mechanism of enzyme inhibition by cyanobacterial toxins.
J.T.Maynes, H.A.Luu, M.M.Cherney, R.J.Andersen, D.Williams, C.F.Holmes, M.N.James.
The microcystins and nodularins are tumour promoting hepatotoxins that are responsible for global adverse human health effects and wildlife fatalities in countries where drinking water supplies contain cyanobacteria. The toxins function by inhibiting broad specificity Ser/Thr protein phosphatases in the host cells, thereby disrupting signal transduction pathways. A previous crystal structure of a microcystin bound to the catalytic subunit of protein phosphatase-1 (PP-1c) showed distinct changes in the active site region when compared with protein phosphatase-1 structures bound to other toxins. We have elucidated the crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (gamma isoform). The atomic structures of these complexes reveal the structural basis for inhibition of protein phosphatases by these toxins. Comparisons of the structures of the cyanobacterial toxin:phosphatase complexes explain the biochemical mechanism by which microcystins but not nodularins permanently modify their protein phosphatase targets by covalent addition to an active site cysteine residue.
  Selected figure(s)  
Figure 1.
Figure 1. Chemical structure of the cyanobacterial toxins. (a) Structure of dihydromicrocystin-LA (MCLA-2H). #The two sites of modification for the microcystins, in MCLA-2H these sites are Leu and Ala and in MCLR these sites are Leu and Arg. *The site of hydrogenation that removes the N-methyldehydroalanine residue and creates an N-methylalanine residue with no Michael addition properties. The 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda) residue includes all of the hydrophobic tail region of the inhibitor. (b) Structure of motuporin (nodularin-V). The Adda residue includes all of the hydrophobic tail region of the inhibitor. (c) Structure of nodularin-R.
Figure 5.
Figure 5. Comparison of PP-1c structures bound to toxins. (a) Stereo representation of the overlay of PP-1c bound to MCLA-2H (blue), MOT (green) and MCLR (orange).15 Motuporin is shown as sticks and the b[12]-b[13] loop is labeled. (b) Stereo representation of the active site regions of the PP-1c-bound toxin structures. The b-methylaspartic acid (Masp), g-linked d-glutamic acid and N-methyldehydroalanine (Nmda) residues are labeled. In MCLA-2H, the N-methylalanine residue and in MOT, the N-methyldehydrobutyrine residues are both in the equivalent position to Nmda. The disulphide bond between the Nmda residue of MCLR and C273 is shown. Colouring is the same as in (a).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 356, 111-120) copyright 2006.  
  Figures were selected by an automated process.  

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.  
20162015 A.Campos, and V.Vasconcelos (2010).
Molecular mechanisms of microcystin toxicity in animal cells.
  Int J Mol Sci, 11, 268-287.  
19906474 E.Lance, M.R.Neffling, C.Gérard, J.Meriluoto, and M.Bormans (2010).
Accumulation of free and covalently bound microcystins in tissues of Lymnaea stagnalis (Gastropoda) following toxic cyanobacteria or dissolved microcystin-LR exposure.
  Environ Pollut, 158, 674-680.  
20411119 I.Sainis, D.Fokas, K.Vareli, A.G.Tzakos, V.Kounnis, and E.Briasoulis (2010).
Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs.
  Mar Drugs, 8, 629-657.  
20219228 W.Okello, V.Ostermaier, C.Portmann, K.Gademann, and R.Kurmayer (2010).
Spatial isolation favours the divergence in microcystin net production by Microcystis in Ugandan freshwater lakes.
  Water Res, 44, 2803-2814.  
20052007 M.A.Labine, and G.Y.Minuk (2009).
Cyanobacterial toxins and liver disease.
  Can J Physiol Pharmacol, 87, 773-788.  
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
18488168 B.Wang, P.Zhang, and Q.Wei (2008).
Recent progress on the structure of Ser/Thr protein phosphatases.
  Sci China C Life Sci, 51, 487-494.  
16962311 V.Neduva, and R.B.Russell (2006).
Peptides mediating interaction networks: new leads at last.
  Curr Opin Biotechnol, 17, 465-471.  
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.