PDBsum entry: 1hi2

Hydrolase

PDB id: 1hi2

Contents

Protein chain

135 a.a. *

Ligands

SO4 ×2

Waters ×110

* Residue conservation analysis

PDB id:

1hi2

Name:

Hydrolase

Title:

Eosinophil-derived neurotoxin (edn) - sulphate 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:

1.6Å R-factor: 0.177 R-free: 0.219

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

Protein chain

P10153  (RNAS2_HUMAN) -  Non-secretory ribonuclease

Seq: 161 a.a.

Struc: 135 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.27.5 - Pancreatic ribonuclease.
• 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 

• Cellular component: extracellular region (2 terms)
• Biological process: chemotaxis (3 terms)
• Biochemical function: nucleic acid binding (6 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.