PDBsum entry 1h1h

Hydrolase

PDB id: 1h1h

Contents

Protein chain

134 a.a. *

Ligands

A2P

Waters ×54

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: 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.
• Authors: C.G.Mohan, E.Boix, H.R.Evans, Z.Nikolovski, M.V.Nogués, C.M.Cuchillo, K.R.Acharya.
• Ref.: Biochemistry, 2002, 41, 12100-12106. [DOI no: 10.1021/bi0264521]
• PubMed id: 12356310

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.