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PDBsum entry 1hi5

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Hydrolase PDB id
1hi5
Jmol
Contents
Protein chain
135 a.a. *
Ligands
ADP
Waters ×132
* Residue conservation analysis
PDB id:
1hi5
Name: Hydrolase
Title: Eosinophil-derived neurotoxin (edn) - adenosine-5'-diphosphate complex
Structure: Eosinophil-derived neurotoxin. Chain: a. Synonym: rnase-2, rnase-us, edn. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Cell: eosinophil. Organelle: granule. Cellular_location: secretory granules. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.8Å     R-factor:   0.193     R-free:   0.253
Authors: D.D.Leonidas,E.Boix,R.Prill,M.Suzuki,R.Turton,K.Minson, G.J.Swaminathan,R.J.Youle,K.R.Acharya
Key ref:
D.D.Leonidas et al. (2001). Mapping the ribonucleolytic active site of eosinophil-derived neurotoxin (EDN). High resolution crystal structures of EDN complexes with adenylic nucleotide inhibitors. J Biol Chem, 276, 15009-15017. PubMed id: 11154698 DOI: 10.1074/jbc.M010585200
Date:
02-Jan-01     Release date:   31-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10153  (RNAS2_HUMAN) -  Non-secretory ribonuclease
Seq:
Struc:
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: E.C.3.1.27.5  - 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   3 terms 
  Biological process     nucleic acid phosphodiester bond hydrolysis   5 terms 
  Biochemical function     nucleic acid binding     7 terms  

 

 
DOI no: 10.1074/jbc.M010585200 J Biol Chem 276:15009-15017 (2001)
PubMed id: 11154698  
 
 
Mapping the ribonucleolytic active site of eosinophil-derived neurotoxin (EDN). High resolution crystal structures of EDN complexes with adenylic nucleotide inhibitors.
D.D.Leonidas, E.Boix, R.Prill, M.Suzuki, R.Turton, K.Minson, G.J.Swaminathan, R.J.Youle, K.R.Acharya.
 
  ABSTRACT  
 
Eosinophil-derived neurotoxin (EDN), a basic ribonuclease found in the large specific granules of eosinophils, belongs to the pancreatic RNase A family. Although its physiological function is still unclear, it has been shown that EDN is a neurotoxin capable of inducing the Gordon phenomenon in rabbits. EDN is also a potent helminthotoxin and can mediate antiviral activity of eosinophils against isolated virions of the respiratory syncytial virus. EDN is a catalytically efficient RNase sharing similar substrate specificity with pancreatic RNase A with its ribonucleolytic activity being absolutely essential for its neurotoxic, helminthotoxic, and antiviral activities. The crystal structure of recombinant human EDN in the unliganded form has been determined previously (Mosimann, S. C., Newton, D. L., Youle, R. J., and James, M. N. G. (1996) J. Mol. Biol. 260, 540-552). We have now determined high resolution (1.8 A) crystal structures for EDN in complex with adenosine-3',5'-diphosphate (3',5'-ADP), adenosine-2',5'-di-phosphate (2',5'-ADP), adenosine-5'-diphosphate (5'-ADP) as well as for a native structure in the presence of sulfate refined at 1.6 A. The inhibition constant of these mononucleotides for EDN has been determined. The structures present the first detailed picture of differences between EDN and RNase A in substrate recognition at the ribonucleolytic active site. They also provide a starting point for the design of tight-binding inhibitors, which may be used to restrain the RNase activity of EDN.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. A, C, and E, diagrams of the 1.8-Å sigmaA 2|F[o]| |F[c]| electron density map of 3',5'-ADP, 2',5'-ADP, and 5'-ADP, respectively. Electron density maps were calculated using the standard protocol as implemented in X-PLOR 3.851 (60) from the EDN model before incorporating the coordinates of each inhibitor, are contoured at the 1.0 level, and the refined structure of the inhibitor is shown. B, D, and F, diagrams showing the interactions of 3',5'-ADP, 2',5'-ADP, and 5'-ADP with EDN, respectively. EDN residues are drawn as ball-and-stick models, water molecules appear as gray spheres, and the nucleotide molecules are shown in dark gray. Hydrogen bonds are indicated by dashed lines.
Figure 4.
Fig. 4. A and C, diagrams of the 1.8-Å sigmaA 2|F[o]| |F[c]| electron density map calculated using the standard protocol as implemented in X-PLOR 3.851 (58) from the EDN model before incorporating the coordinates of sulfates A and B, respectively. The map is contoured at the 1.0 level. The EDN residues are shown in light gray. B and D, diagrams showing the interactions of sulfate ions A and B with EDN, respectively. EDN residues are drawn as ball-and-stick models, water molecules appear as dark gray spheres, and the sulfate molecules are shown in black. Hydrogen bonds are indicated by dashed lines. Diagrams were drawn with BOBSCRIPT (61).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 15009-15017) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20213669 M.Torrent, M.V.Nogués, and E.Boix (2011).
Eosinophil cationic protein (ECP) can bind heparin and other glycosaminoglycans through its RNase active site.
  J Mol Recognit, 24, 90.  
19191310 D.E.Holloway, G.B.Chavali, D.D.Leonidas, M.D.Baker, and K.R.Acharya (2009).
Influence of naturally-occurring 5'-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: An X-ray crystallographic study.
  Biopolymers, 91, 995.
PDB codes: 2w5g 2w5i 2w5k 2w5l 2w5m
19090717 D.Sikriwal, D.Seth, and J.K.Batra (2009).
Role of catalytic and non-catalytic subsite residues in ribonuclease activity of human eosinophil-derived neurotoxin.
  Biol Chem, 390, 225-234.  
18694936 M.Ulrich, A.Petre, N.Youhnovski, F.Prömm, M.Schirle, M.Schumm, R.S.Pero, A.Doyle, J.Checkel, H.Kita, N.Thiyagarajan, K.R.Acharya, P.Schmid-Grendelmeier, H.U.Simon, H.Schwarz, M.Tsutsui, H.Shimokawa, G.Bellon, J.J.Lee, M.Przybylski, and G.Döring (2008).
Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase.
  J Biol Chem, 283, 28629-28640.  
17483910 D.Sikriwal, D.Seth, P.Dey, and J.K.Batra (2007).
Human eosinophil-derived neurotoxin: involvement of a putative non-catalytic phosphate-binding subsite in its catalysis.
  Mol Cell Biochem, 303, 175-181.  
17460791 E.Boix, and M.V.Nogués (2007).
Mammalian antimicrobial proteins and peptides: overview on the RNase A superfamily members involved in innate host defence.
  Mol Biosyst, 3, 317-335.  
14573867 D.D.Leonidas, G.B.Chavali, N.G.Oikonomakos, E.D.Chrysina, M.N.Kosmopoulou, M.Vlassi, C.Frankling, and K.R.Acharya (2003).
High-resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors.
  Protein Sci, 12, 2559-2574.
PDB codes: 1o0f 1o0h 1o0m 1o0n 1o0o
12356310 C.G.Mohan, E.Boix, H.R.Evans, Z.Nikolovski, M.V.Nogués, C.M.Cuchillo, and K.R.Acharya (2002).
The crystal structure of eosinophil cationic protein in complex with 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic active site.
  Biochemistry, 41, 12100-12106.
PDB code: 1h1h
11876642 G.J.Swaminathan, D.E.Holloway, K.Veluraja, and K.R.Acharya (2002).
Atomic resolution (0.98 A) structure of eosinophil-derived neurotoxin.
  Biochemistry, 41, 3341-3352.
PDB code: 1gqv
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.