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Glycosidase PDB id
1apg
Jmol
Contents
Protein chain
267 a.a. *
Ligands
__A-__G
* Residue conservation analysis
Superseded by: 3rtj
PDB id:
1apg
Name: Glycosidase
Title: X-ray analysis of substrate analogs in the ricin a-chain act
Structure: RNA (5'-r( Ap G)-3'). Chain: d. Engineered: yes. Ricin. Chain: a. Engineered: yes
Source: Synthetic: yes. Ricinus communis. Castor bean. Organism_taxid: 3988
Resolution:
3.00Å     R-factor:   0.198    
Authors: A.F.Monzingo,J.D.Robertus
Key ref:
A.F.Monzingo and J.D.Robertus (1992). X-ray analysis of substrate analogs in the ricin A-chain active site. J Mol Biol, 227, 1136-1145. PubMed id: 1433290 DOI: 10.1016/0022-2836(92)90526-P
Date:
16-Jun-92     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     negative regulation of translation   1 term 
  Biochemical function     rRNA N-glycosylase activity     1 term  

 

 
DOI no: 10.1016/0022-2836(92)90526-P J Mol Biol 227:1136-1145 (1992)
PubMed id: 1433290  
 
 
X-ray analysis of substrate analogs in the ricin A-chain active site.
A.F.Monzingo, J.D.Robertus.
 
  ABSTRACT  
 
Ricin A-chain is an N-glycosidase that hydrolyzes the adenine ring from a specific adenosine of rRNA. Formycin monophosphate (FMP) and adenyl(3'-->5')guanosine (ApG) were bound to ricin A-chain and their structures elucidated by X-ray crystallography. The formycin ring stacks between tyrosines 80 and 123 and at least four hydrogen bonds are made to the adenine moiety. A residue invariant in this enzyme class, Arg180, appears to hydrogen bond to N-3 of the susceptible adenine. Three hypothetical models for binding a true hexanucleotide substrate, CGAGAG, are proposed. They incorporate adenine binding, shown by crystallography, but also include geometry likely to favor catalysis. For example, efforts have been made to orient the ribose ring in a way that allows solvent attack and oxycarbonium stabilization by the enzyme. The favored model is a simple perturbation of the tetraloop structure determined by nuclear magnetic resonance for similar polynucleotides. The model is attractive in that specific roles are defined for conserved protein residues. A mechanism of action is proposed. It invokes oxycarbonium ion stabilization on ribose by Glu177 in the transition state. Arg180 stabilizes anion development on the leaving adenine by protonation at N-3 and may activate a trapped water molecule that is the ultimate nucleophile in the depurination.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. FMP and key active site residues of RTA superiposed on the omit map electron density. Klectron ensity for the purine ring of FMP lies near te center of the picture and extends the phosphate group at th lower right-hand corner. The map is at 2.8 .& esolution and 15% of the cell volume ies within the density baskets. 		Figure 5.
Figure 5. ApG and key active site residues of RTA superimposed on the omit map electron density. Denity for the adenine ring of the dinucleotide is near the upper center of the Figure. The guanine base is nearly edge-on along the botom right. The map is at 3 A resolution and 20% of the cell volume lies within the density baskes.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 1136-1145) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19920175 M.C.Ho, M.B.Sturm, S.C.Almo, and V.L.Schramm (2009).
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins.
  Proc Natl Acad Sci U S A, 106, 20276-20281.
PDB codes: 3hio 3hiq 3his 3hit 3hiv 3hiw
17308345 D.S.Chan, L.O.Chu, K.M.Lee, P.H.Too, K.W.Ma, K.H.Sze, G.Zhu, P.C.Shaw, and K.B.Wong (2007).
Interaction between trichosanthin, a ribosome-inactivating protein, and the ribosomal stalk protein P2 by chemical shift perturbation and mutagenesis analyses.
  Nucleic Acids Res, 35, 1660-1672.  
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
17477546 S.Roday, S.Saen-oon, and V.L.Schramm (2007).
Vinyldeoxyadenosine in a sarcin-ricin RNA loop and its binding to ricin toxin a-chain.
  Biochemistry, 46, 6169-6182.  
17470286 X.Hou, M.Chen, L.Chen, E.J.Meehan, J.Xie, and M.Huang (2007).
X-ray sequence and crystal structure of luffaculin 1, a novel type 1 ribosome-inactivating protein.
  BMC Struct Biol, 7, 29.
PDB code: 2oqa
17101666 X.P.Li, M.Baricevic, H.Saidasan, and N.E.Tumer (2007).
Ribosome depurination is not sufficient for ricin-mediated cell death in Saccharomyces cerevisiae.
  Infect Immun, 75, 417-428.  
16772301 A.Bagaria, K.Surendranath, U.A.Ramagopal, S.Ramakumar, and A.A.Karande (2006).
Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin.
  J Biol Chem, 281, 34465-34474.
PDB codes: 2amz 2q3n
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.  
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.  
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
15304562 K.A.Hudak, B.A.Parikh, R.Di, M.Baricevic, M.Santana, M.Seskar, and N.E.Tumer (2004).
Generation of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: evidence that ribosome depurination is not sufficient for cytotoxicity.
  Nucleic Acids Res, 32, 4244-4256.  
12823544 H.Niwa, A.G.Tonevitsky, I.I.Agapov, S.Saward, U.Pfüller, and R.A.Palmer (2003).
Crystal structure at 3 A of mistletoe lectin I, a dimeric type-II ribosome-inactivating protein, complexed with galactose.
  Eur J Biochem, 270, 2739-2749.
PDB code: 1oql
12466280 S.Bagga, D.Seth, and J.K.Batra (2003).
The cytotoxic activity of ribosome-inactivating protein saporin-6 is attributed to its rRNA N-glycosidase and internucleosomal DNA fragmentation activities.
  J Biol Chem, 278, 4813-4820.  
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
11337416 K.Nielsen, and R.S.Boston (2001).
RIBOSOME-INACTIVATING PROTEINS: A Plant Perspective.
  Annu Rev Plant Physiol Plant Mol Biol, 52, 785-816.  
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.  
11551434 M.A.Olson (2001).
Electrostatic effects on the free-energy balance in folding a ribosome-inactivating protein.
  Biophys Chem, 91, 219-229.  
11418185 S.Tang, L.Xie, F.Hou, W.Y.Liu, and K.Ruan (2001).
Non-specific deadenylation and deguanylation of naked RNA catalyzed by ricin under acidic condition.
  Biochim Biophys Acta, 1519, 192-198.  
10636890 C.L.Liu, C.C.Tsai, S.C.Lin, L.I.Wang, C.I.Hsu, M.J.Hwang, and J.Y.Lin (2000).
Primary structure and function analysis of the Abrus precatorius agglutinin A chain by site-directed mutagenesis. Pro(199) Of amphiphilic alpha-helix H impairs protein synthesis inhibitory activity.
  J Biol Chem, 275, 1897-1901.  
10652330 F.Rajamohan, M.J.Pugmire, I.V.Kurinov, and F.M.Uckun (2000).
Modeling and alanine scanning mutagenesis studies of recombinant pokeweed antiviral protein.
  J Biol Chem, 275, 3382-3390.  
10871371 M.Brigotti, D.Carnicelli, P.Accorsi, S.Rizzi, L.Montanaro, and S.Sperti (2000).
4-Aminopyrazolo[3,4-d]pyrimidine (4-APP) as a novel inhibitor of the RNA and DNA depurination induced by Shiga toxin 1.
  Nucleic Acids Res, 28, 2383-2388.  
11030435 S.Tang, R.G.Hu, W.Y.Liu, and K.C.Ruan (2000).
Non-specific depurination activity of saporin-S6, a ribosome-inactivating protein, under acidic conditions.
  Biol Chem, 381, 769-772.  
10737925 Y.J.Gu, and Z.X.Xia (2000).
Crystal structures of the complexes of trichosanthin with four substrate analogs and catalytic mechanism of RNA N-glycosidase.
  Proteins, 39, 37-46.
PDB code: 1qd2
  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
  10595542 I.V.Kurinov, F.Rajamohan, T.K.Venkatachalam, and F.M.Uckun (1999).
X-ray crystallographic analysis of the structural basis for the interaction of pokeweed antiviral protein with guanine residues of ribosomal RNA.
  Protein Sci, 8, 2399-2405.
PDB code: 1d6a
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.  
10329776 Y.R.Yuan, Y.N.He, J.P.Xiong, and Z.X.Xia (1999).
Three-dimensional structure of beta-momorcharin at 2.55 A resolution.
  Acta Crystallogr D Biol Crystallogr, 55, 1144-1151.
PDB code: 1cf5
10571185 Y.X.Wang, N.Neamati, J.Jacob, I.Palmer, S.J.Stahl, J.D.Kaufman, P.L.Huang, P.L.Huang, H.E.Winslow, Y.Pommier, P.T.Wingfield, S.Lee-Huang, A.Bax, and D.A.Torchia (1999).
Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions.
  Cell, 99, 433-442.
PDB code: 1d8v
9649321 J.K.Suh, C.J.Hovde, and J.D.Robertus (1998).
Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes.
  Biochemistry, 37, 9394-9398.  
9572842 M.Degano, S.C.Almo, J.C.Sacchettini, and V.L.Schramm (1998).
Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
  Biochemistry, 37, 6277-6285.
PDB code: 2mas
18726203 S.Wu, X.Lu, Y.Zhu, J.Yang, and Y.Dong (1998).
N-glycosidase mechanism of Trichosanthin.
  Sci China C Life Sci, 41, 174-180.  
  9782053 T.Hermann, and E.Westhof (1998).
Exploration of metal ion binding sites in RNA folds by Brownian-dynamics simulations.
  Structure, 6, 1303-1314.  
9708998 X.Y.Chen, T.M.Link, and V.L.Schramm (1998).
Ricin A-chain: kinetics, mechanism, and RNA stem-loop inhibitors.
  Biochemistry, 37, 11605-11613.  
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.  
9692198 Y.Minami, K.Yamaguchi, F.Yagi, K.Tadera, and G.Funatsu (1998).
Isolation and amino acid sequence of a protein-synthesis inhibitor from the seeds of rye (Secale cereale).
  Biosci Biotechnol Biochem, 62, 1152-1156.  
9648227 Y.Minami, M.R.Islam, and G.Funatsu (1998).
Chemical modifications of momordin-a and luffin-a, ribosome-inactivating proteins from the seeds of Momordica charantia and Luffa cylindrica: involvement of His140, Tyr165, and Lys231 in the protein-synthesis inhibitory activity.
  Biosci Biotechnol Biochem, 62, 959-964.  
18726259 Z.Zeng, L.Jin, H.Li, Z.Hu, and D.Wang (1998).
Crystal structure of pokeweed antiviral protein from seeds ofPhytolacca americana at 0.25 nm.
  Sci China C Life Sci, 41, 413-418.  
9037714 M.A.Olson (1997).
Ricin A-chain structural determinant for binding substrate analogues: a molecular dynamics simulation analysis.
  Proteins, 27, 80-95.  
  9667869 V.L.Schramm (1997).
Enzymatic N-riboside scission in RNA and RNA precursors.
  Curr Opin Chem Biol, 1, 323-331.  
8604301 M.Orita, F.Nishikawa, T.Kohno, T.Senda, Y.Mitsui, E.Yaeta, T.Kazunari, and S.Nishikawa (1996).
High-resolution NMR study of a GdAGA tetranucleotide loop that is an improved substrate for ricin, a cytotoxic plant protein.
  Nucleic Acids Res, 24, 611-618.  
8780513 P.J.Day, S.R.Ernst, A.E.Frankel, A.F.Monzingo, J.M.Pascal, M.C.Molina-Svinth, and J.D.Robertus (1996).
Structure and activity of an active site substitution of ricin A chain.
  Biochemistry, 35, 11098-11103.
PDB codes: 1obs 1obt
7759553 C.A.Vater, L.M.Bartle, J.D.Leszyk, J.M.Lambert, and V.S.Goldmacher (1995).
Ricin A chain can be chemically cross-linked to the mammalian ribosomal proteins L9 and L10e.
  J Biol Chem, 270, 12933-12940.  
7576081 J.P.Xiong, Z.X.Xia, and Y.Wang (1995).
Identification of a stable complex of trichosanthin with nicotinamide adenine dinucleotide phosphate.
  J Protein Chem, 14, 139-144.  
7561975 M.A.Olson, J.P.Scovill, and D.C.Hack (1995).
Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.
  J Comput Aided Mol Des, 9, 226-236.  
8539247 T.Kohno, T.Senda, H.Narumi, S.Kimura, and Y.Mitsui (1995).
Crystallization and preliminary crystallographic analysis of recombinant abrin-a A-chain with ribosome inactivating activity.
  Proteins, 23, 126-127.  
8581322 W.L.Thompson, J.P.Scovill, and J.G.Pace (1995).
Drugs that show protective effects from ricin toxicity in in vitro protein synthesis assays.
  Nat Toxins, 3, 369-377.  
8867881 W.Y.Chan, T.B.Ng, and P.C.Shaw (1995).
Mouse embryonic development and tumor cell growth under the influence of recombinant trichosanthin (a ribosome inactivating protein) and its muteins.
  Teratog Carcinog Mutagen, 15, 259-268.  
7667309 Y.Hur, D.J.Hwang, O.Zoubenko, C.Coetzer, F.M.Uckun, and N.E.Tumer (1995).
Isolation and characterization of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: identification of residues important for toxicity.
  Proc Natl Acad Sci U S A, 92, 8448-8452.  
7925458 H.Ago, J.Kataoka, H.Tsuge, N.Habuka, E.Inagaki, M.Noma, and M.Miyano (1994).
X-ray structure of a pokeweed antiviral protein, coded by a new genomic clone, at 0.23 nm resolution. A model structure provides a suitable electrostatic field for substrate binding.
  Eur J Biochem, 225, 369-374.
PDB code: 1apa
7634073 J.P.Xiong, Z.X.Xia, and Y.Wang (1994).
Crystal structure of trichosanthin-NADPH complex at 1.7 A resolution reveals active-site architecture.
  Nat Struct Biol, 1, 695-700.
PDB code: 1tcs
  8075985 J.Ren, Y.Wang, Y.Dong, and D.I.Stuart (1994).
The N-glycosidase mechanism of ribosome-inactivating proteins implied by crystal structures of alpha-momorcharin.
  Structure, 2, 7.
PDB codes: 1aha 1ahb 1ahc
8052614 K.N.Morris, and I.G.Wool (1994).
Analysis of the contribution of an amphiphilic alpha-helix to the structure and to the function of ricin A chain.
  Proc Natl Acad Sci U S A, 91, 7530-7533.  
8415744 A.A.Szewczak, P.B.Moore, Y.L.Chang, and I.G.Wool (1993).
The conformation of the sarcin/ricin loop from 28S ribosomal RNA.
  Proc Natl Acad Sci U S A, 90, 9581-9585.
PDB code: 1scl
7694230 A.Kajava, and H.Rüterjans (1993).
Molecular modelling of the 3-D structure of RNA tetraloops with different nucleotide sequences.
  Nucleic Acids Res, 21, 4556-4562.  
  8453380 D.Mlsna, A.F.Monzingo, B.J.Katzin, S.Ernst, and J.D.Robertus (1993).
Structure of recombinant ricin A chain at 2.3 A.
  Protein Sci, 2, 429-435.
PDB code: 1rtc
8284214 M.Orita, F.Nishikawa, T.Shimayama, K.Taira, Y.Endo, and S.Nishikawa (1993).
High-resolution NMR study of a synthetic oligoribonucleotide with a tetranucleotide GAGA loop that is a substrate for the cytotoxic protein, ricin.
  Nucleic Acids Res, 21, 5670-5678.  
  1492120 J.D.Irvin, and F.M.Uckun (1992).
Pokeweed antiviral protein: ribosome inactivation and therapeutic applications.
  Pharmacol Ther, 55, 279-302.  
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.