PDBsum entry 2bex

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Hydrolase/inhibitor PDB id
Protein chains
456 a.a. *
135 a.a. *
Waters ×616
* Residue conservation analysis
PDB id:
Name: Hydrolase/inhibitor
Title: Crystal structure of placental ribonuclease inhibitor in complex with human eosinophil derived neurotoxin at 2a resolution
Structure: Ribonuclease inhibitor. Chain: a, b. Synonym: ribonuclease/angiogenin inhibitor, rai, ri, rnase inhibitor. Nonsecretory ribonuclease. Chain: c, d. Synonym: eosinophil derived neurotoxin, ribonuclease us, rnase upi-2, ribonuclease 2, rnase 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: placenta. Tissue: blood. Cell: eosinophils. Expressed in: escherichia coli. Expression_system_taxid: 562
1.99Å     R-factor:   0.205     R-free:   0.243
Authors: S.Iyer,D.E.Holloway,K.Kumar,R.Shapiro,K.R.Acharya
Key ref:
S.Iyer et al. (2005). Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor. J Mol Biol, 347, 637-655. PubMed id: 15755456 DOI: 10.1016/j.jmb.2005.01.035
01-Dec-04     Release date:   17-Mar-05    
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Protein chains
Pfam   ArchSchema ?
P13489  (RINI_HUMAN) -  Ribonuclease inhibitor
461 a.a.
456 a.a.
Protein chains
Pfam   ArchSchema ?
P10153  (RNAS2_HUMAN) -  Non-secretory ribonuclease
161 a.a.
135 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains C, D: E.C.  - Pancreatic ribonuclease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     nucleic acid phosphodiester bond hydrolysis   8 terms 
  Biochemical function     protein binding     9 terms  


DOI no: 10.1016/j.jmb.2005.01.035 J Mol Biol 347:637-655 (2005)
PubMed id: 15755456  
Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor.
S.Iyer, D.E.Holloway, K.Kumar, R.Shapiro, K.R.Acharya.
Placental ribonuclease inhibitor (RI) binds diverse mammalian RNases with dissociation constants that are in the femtomolar range. Previous studies on the complexes of RI with RNase A and angiogenin revealed that RI utilises largely distinctive interactions to achieve high affinity for these two ligands. Here we report a 2.0 angstroms resolution crystal structure of RI in complex with a third ligand, eosinophil-derived neurotoxin (EDN), and a mutational analysis based on this structure. The RI-EDN interface is more extensive than those of the other two complexes and contains a considerably larger set of interactions. Few of the contacts present in the RI-angiogenin complex are replicated; the correspondence to the RI-RNase A complex is somewhat greater, but still modest. The energetic contributions of various interface regions differ strikingly from those in the earlier complexes. These findings provide insight into the structural basis for the unusual combination of high avidity and relaxed stringency that RI displays.
  Selected figure(s)  
Figure 1.
Figure 1. (a) Ribbon representation of the hRI-EDN complex, drawn with the program MOLSCRIPT.58 The hRI molecule has been coloured purple and the EDN molecule is shown in olive green. (b) Stereo view of the superposed C^a traces of the hRI-EDN complex (purple), the pRI-RNase A complex18 (olive green) and the hRI-Ang complex12 (cyan). Superpositioning was performed by aligning the RI components of the respective complexes. (c) Stereo view of the superposition of C^a traces of the two hRI molecules in the asymmetric unit. hRI from Complex 1 is coloured purple and the hRI from Complex 2 is shown in blue. (d) Molecular surfaces of the inhibitor (left panel) and the enzymes (right panel) from the different RI complexes. The horseshoe was rotated by vert, similar 20° from the standard orientation (b) in order to better show the interface. The enzymes were rotated by about 180°, along the x-axis, from the standard orientation (b) to show their binding interface. The surfaces have been colour coded according to the type of contact atoms at the interface. Non-polar atoms are coloured green, uncharged polar atoms are shown in blue and charged atoms in red. The program GRASP was used to draw the molecular surfaces.59
Figure 3.
Figure 3. Amino acid sequence alignments for hRI and pRI (top) and for EDN, Ang, and RNase A (bottom), drawn by using the program ALSCRIPT.60 The pRI sequence shows contact residues for RNase A shaded in black. The hRI sequence shows contact residues unique for Ang and EDN boxed in black and grey, respectively; those common to both have been boxed in white. Contact residues on EDN, Ang, and RNase A are boxed in black. The beginning of each repeat unit is marked for hRI.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 347, 637-655) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19452560 K.L.Hindle, J.Bella, and S.C.Lovell (2009).
Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.
  Proteins, 77, 342-358.  
18673284 T.J.Rutkoski, and R.T.Raines (2008).
Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.
  Curr Pharm Biotechnol, 9, 185-189.  
17350650 R.J.Johnson, J.G.McCoy, C.A.Bingman, G.N.Phillips, and R.T.Raines (2007).
Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein.
  J Mol Biol, 368, 434-449.
PDB codes: 1z7x 2q4g
17956129 R.J.Johnson, L.D.Lavis, and R.T.Raines (2007).
Intraspecies regulation of ribonucleolytic activity.
  Biochemistry, 46, 13131-13140.  
16803891 T.Nitto, K.D.Dyer, M.Czapiga, and H.F.Rosenberg (2006).
Evolution and function of leukocyte RNase A ribonucleases of the avian species, Gallus gallus.
  J Biol Chem, 281, 25622-25634.  
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