PDBsum entry 2c01

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protein ligands links
Hydrolase PDB id
Protein chain
135 a.a. *
Waters ×238
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structures of eosinophil-derived neurotoxin in complex with the inhibitors 5'-atp, ap3a, ap4a and ap5a
Structure: Nonsecretory ribonuclease. Chain: x. Synonym: eosinophil-derived neurotoxin, ribonuclease us, rnase upi-2, ribonuclease 2, rnase 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: eosinophil. Expressed in: escherichia coli. Expression_system_taxid: 562
1.24Å     R-factor:   0.188     R-free:   0.221
Authors: M.D.Baker,D.E.Holloway,G.J.Swaminathan,K.R.Acharya
Key ref:
M.D.Baker et al. (2006). Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A. Biochemistry, 45, 416-426. PubMed id: 16401072 DOI: 10.1021/bi0518592
24-Aug-05     Release date:   18-Jan-06    
Go to PROCHECK summary

Protein chain
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: 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   3 terms 
  Biological process     nucleic acid phosphodiester bond hydrolysis   5 terms 
  Biochemical function     nucleic acid binding     6 terms  


DOI no: 10.1021/bi0518592 Biochemistry 45:416-426 (2006)
PubMed id: 16401072  
Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.
M.D.Baker, D.E.Holloway, G.J.Swaminathan, K.R.Acharya.
Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. To probe the importance of this enzymatic activity further, specific inhibitors will be of great aid. Derivatives of 5'-ADP are among the most potent inhibitors currently known. Here, we use X-ray crystallography to investigate the binding of four natural nucleotides containing this moiety. 5'-ATP binds in two alternative orientations, one occupying the B2 subsite in a conventional manner and one being a retro orientation with no ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined conformation, and a disordered second adenosine moiety. Diadenosine pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a completely ordered fashion with one adenine positioned conventionally at the B2 subsite, the polyphosphate chain occupying the P1 and putative P(-1) subsites, and the other adenine bound in a retro-like manner at the edge of the B1 subsite. The binding mode of each of these inhibitors has features seen in previously determined structures of adenosine diphosphates. We examine the structure-affinity relationships of these inhibitors and discuss the implications for the design of improved inhibitors.

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.  
20714505 N.Stern, D.T.Major, H.E.Gottlieb, D.Weizman, and B.Fischer (2010).
What is the conformation of physiologically-active dinucleoside polyphosphates in solution? Conformational analysis of free dinucleoside polyphosphates by NMR and molecular dynamics simulations.
  Org Biomol Chem, 8, 4637-4652.  
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
19189375 D.V.Laurents, M.Bruix, M.A.Jiménez, J.Santoro, E.Boix, M.Moussaoui, M.V.Nogués, and M.Rico (2009).
The (1)H, (13)C, (15)N resonance assignment, solution structure, and residue level stability of eosinophil cationic protein/RNase 3 determined by NMR spectroscopy.
  Biopolymers, 91, 1018-1028.
PDB code: 2kb5
17894350 D.K.Simanshu, H.S.Savithri, and M.R.Murthy (2008).
Crystal structures of Salmonella typhimurium propionate kinase and its complex with Ap4A: evidence for a novel Ap4A synthetic activity.
  Proteins, 70, 1379-1388.
PDB codes: 2e1y 2e1z 2e20
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.  
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