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PDBsum entry 1br5
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protein ligands links
Hydrolase PDB id
1br5

 

 

 

 

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Contents
Protein chain
267 a.a. *
Ligands
NEO
Waters ×55
* Residue conservation analysis
PDB id:
1br5
Name: Hydrolase
Title: Ricin a chain (recombinant) complex with neopterin
Structure: Protein (ricin). Chain: a. Synonym: rta. Engineered: yes
Source: Ricinus communis. Castor bean. Organism_taxid: 3988. Organ: seed. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.50Å     R-factor:   0.194    
Authors: P.Day,X.Yan,T.Hollis,M.Svinth,A.F.Monzingo,G.W.A.Milne,J.D.Robertus
Key ref:
X.Yan et al. (1997). Structure-based identification of a ricin inhibitor. J Mol Biol, 266, 1043-1049. PubMed id: 9086280 DOI: 10.1006/jmbi.1996.0865
Date:
26-Aug-98     Release date:   02-Sep-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P02879  (RICI_RICCO) -  Ricin from Ricinus communis
Seq:
Struc: 		 
Seq:
Struc: 		576 a.a.
267 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.2.2.22  - rRNA N-glycosylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.

 

 
DOI no: 10.1006/jmbi.1996.0865 J Mol Biol 266:1043-1049 (1997)
PubMed id: 9086280  
 
 
Structure-based identification of a ricin inhibitor.
X.Yan, T.Hollis, M.Svinth, P.Day, A.F.Monzingo, G.W.Milne, J.D.Robertus.
 
  ABSTRACT  
 
Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assisted searches indicated that pterins might bind in the RTA active site which normally recognizes a specific adenine base on rRNA. Kinetic assays showed that pteroic acid could inhibit RTA activity with an apparent Ki of 0.6 mM. A 2.3 A crystal structure of the complex revealed the mode of binding. The pterin ring displaces Tyr80 and binds in the adenine pocket making specific hydrogen bonds to active site residues. The benzoate moiety of pteroic acid binds on the opposite side of Tyr80 making van der Waals contact with the Tyr ring and forming a hydrogen bond with Asn78. Neopterin, a propane triol derivative of pterin, also binds to RTA as revealed by the X-ray structure of its complex with RTA. Neither pterin-6-carboxylic acid nor folic acid bind to the crystal or act as inhibitors. The models observed suggest alterations to the pterin moiety which may produce more potent and specific RTA inhibitors.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Interactions between pteroic acid and RTA. Hydrogen bonds are shown as broken lines with the lengths indicated. 		Figure 5.
Figure 5. Binding of neopterin in the RTA active site. Hydrogen bonds are shown as broken lines and the lengths are indicated.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 266, 1043-1049) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20436939 J.M.Pruet, J.D.Robertus, and E.V.Anslyn (2010).
Acyl radical insertion for the direct formation of new 7-substituted pterin analogs.
  Tetrahedron Lett, 51, 2539-2540.  
20354892 J.R.Greenwood, D.Calkins, A.P.Sullivan, and J.C.Shelley (2010).
Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution.
  J Comput Aided Mol Des, 24, 591-604.  
  19812763 A.T.Zemla, and C.L.Ecale Zhou (2008).
Structural re-alignment in an immunogenic surface region of ricin a chain.
  Bioinform Biol Insights, 2, 5.  
18196462 J.Kirchmair, P.Markt, S.Distinto, G.Wolber, and T.Langer (2008).
Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection--what can we learn from earlier mistakes?
  J Comput Aided Mol Des, 22, 213-228.  
17892319 C.Chennubhotla, and I.Bahar (2007).
Signal propagation in proteins and relation to equilibrium fluctuations.
  PLoS Comput Biol, 3, 1716-1726.  
17986339 J.H.Carra, C.A.McHugh, S.Mulligan, L.M.Machiesky, A.S.Soares, and C.B.Millard (2007).
Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site.
  BMC Struct Biol, 7, 72.
PDB codes: 2p8n 2pjn 2pjo 2r2x 2r3d
17311346 S.Sacquin-Mora, E.Laforet, and R.Lavery (2007).
Locating the active sites of enzymes using mechanical properties.
  Proteins, 67, 350-359.  
15889996 C.J.Marsden, D.C.Smith, L.M.Roberts, and J.M.Lord (2005).
Ricin: current understanding and prospects for an antiricin vaccine.
  Expert Rev Vaccines, 4, 229-237.  
15905278 C.L.Zhou, A.T.Zemla, D.Roe, M.Young, M.Lam, J.S.Schoeniger, and R.Balhorn (2005).
Computational approaches for identification of conserved/unique binding pockets in the A chain of ricin.
  Bioinformatics, 21, 3089-3096.  
15803193 J.C.Burnett, E.A.Henchal, A.L.Schmaljohn, and S.Bavari (2005).
The evolving field of biodefence: therapeutic developments and diagnostics.
  Nat Rev Drug Discov, 4, 281-297.  
15939021 L.W.Yang, and I.Bahar (2005).
Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.
  Structure, 13, 893-904.  
15774467 V.Mishra, S.Bilgrami, R.S.Sharma, P.Kaur, S.Yadav, R.Krauspenhaar, C.Betzel, W.Voelter, C.R.Babu, and T.P.Singh (2005).
Crystal structure of himalayan mistletoe ribosome-inactivating protein reveals the presence of a natural inhibitor and a new functionally active sugar-binding site.
  J Biol Chem, 280, 20712-20721.
PDB code: 1yf8
14686928 C.J.Marsden, V.Fülöp, P.J.Day, and J.M.Lord (2004).
The effect of mutations surrounding and within the active site on the catalytic activity of ricin A chain.
  Eur J Biochem, 271, 153-162.
PDB codes: 1uq4 1uq5
15372082 G.J.Rainey, and J.A.Young (2004).
Antitoxins: novel strategies to target agents of bioterrorism.
  Nat Rev Microbiol, 2, 721-726.  
15224385 H.Matter, and P.Kotsonis (2004).
Biology and chemistry of the inhibition of nitric oxide synthases by pteridine-derivatives as therapeutic agents.
  Med Res Rev, 24, 662-684.  
15489170 R.F.Fischetti, D.J.Rodi, D.B.Gore, and L.Makowski (2004).
Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins.
  Chem Biol, 11, 1431-1443.  
11288182 J.M.Pascal, P.J.Day, A.F.Monzingo, S.R.Ernst, J.D.Robertus, R.Iglesias, Y.Pérez, J.M.Férreras, L.Citores, and T.Girbés (2001).
2.8-A crystal structure of a nontoxic type-II ribosome-inactivating protein, ebulin l.
  Proteins, 43, 319-326.
PDB codes: 1hwm 1hwn 1hwo 1hwp
11389598 K.S.Tanaka, X.Y.Chen, Y.Ichikawa, P.C.Tyler, R.H.Furneaux, and V.L.Schramm (2001).
Ricin A-chain inhibitors resembling the oxacarbenium ion transition state.
  Biochemistry, 40, 6845-6851.  
10671531 J.R.Hesselberth, D.Miller, J.Robertus, and A.D.Ellington (2000).
In vitro selection of RNA molecules that inhibit the activity of ricin A-chain.
  J Biol Chem, 275, 4937-4942.  
  10493577 I.V.Kurinov, D.E.Myers, J.D.Irvin, and F.M.Uckun (1999).
X-ray crystallographic analysis of the structural basis for the interactions of pokeweed antiviral protein with its active site inhibitor and ribosomal RNA substrate analogs.
  Protein Sci, 8, 1765-1772.
PDB codes: 1qcg 1qci 1qcj
9876120 M.A.Olson, and L.Cuff (1999).
Free energy determinants of binding the rRNA substrate and small ligands to ricin A-chain.
  Biophys J, 76, 28-39.  
10446182 S.Ghosh, D.Wolan, S.Adak, B.R.Crane, N.S.Kwon, J.A.Tainer, E.D.Getzoff, and D.J.Stuehr (1999).
Mutational analysis of the tetrahydrobiopterin-binding site in inducible nitric-oxide synthase.
  J Biol Chem, 274, 24100-24112.  
9875848 C.S.Raman, H.Li, P.Martásek, V.Král, B.S.Masters, and T.L.Poulos (1998).
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.
  Cell, 95, 939-950.
PDB codes: 1nse 2nse 3nse 4nse
9552157 X.Yan, P.Day, T.Hollis, A.F.Monzingo, E.Schelp, J.D.Robertus, G.W.Milne, and S.Wang (1998).
Recognition and interaction of small rings with the ricin A-chain binding site.
  Proteins, 31, 33-41.  
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.

 

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