1H1H

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

Summary for 1H1H

• Entry DOI: 10.2210/pdb1h1h/pdb
• Related: 1DYT 1QMT
• Descriptor: EOSINOPHIL CATIONIC PROTEIN, ADENOSINE-2'-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: hydrolase, eosinophil cationic protein, eosinophil derived neurotoxin, adenosine-2', 5'-diphosphate, ribonuclease, toxin
• Biological source: HOMO SAPIENS
• Total number of polymer chains: 1
• Total formula weight: 16157.27

Authors

Mohan, C.G.,Boix, E.,Evans, H.R.,Nikolovski, Z.,Nogues, M.V.,Cuchillo, C.M.,Acharya, K.R. (deposition date: 2002-07-15, release date: 2002-10-03, Last modification date: 2024-11-20)

Primary citation

Mohan, C.G.,Boix, E.,Evans, H.R.,Nikolovski, Z.,Nogues, M.V.,Cuchillo, C.M.,Acharya, K.R.
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-, 2002

PubMed Abstract: Eosinophil cationic protein (ECP) is a component of the eosinophil granule matrix. It shows marked toxicity against helminth parasites, bacteria single-stranded RNA viruses, and host epithelial cells. Secretion of human ECP is related to eosinophil-associated allergic, asthmatic, and inflammatory diseases. ECP belongs to the pancreatic ribonuclease superfamily of proteins, and the crystal structure of ECP in the unliganded form (determined previously) exhibited a conserved RNase A fold [Boix, E., et al. (1999) Biochemistry 38, 16794-16801]. We have now determined a high-resolution (2.0 A) crystal structure of ECP in complex with adenosine 2',5'-diphosphate (2',5'-ADP) which has revealed the details of the ribonucleolytic active site. Residues Gln-14, His-15, and Lys-38 make hydrogen bond interactions with the phosphate at the P(1) site, while His-128 interacts with the purine ring at the B(2) site. A new phosphate binding site, P(-)(1), has been identified which involves Arg-34. This study is the first detailed structural analysis of the nucleotide recognition site in ECP and provides a starting point for the understanding of its substrate specificity and low catalytic efficiency compared with that of the eosinophil-derived neurotoxin (EDN), a close homologue.

PubMed: 12356310
DOI: 10.1021/BI0264521

Experimental method

X-RAY DIFFRACTION (2 Å)