Naslov
The Crystal Structure of Eosinophil Cationic Protein in Complex with 2‘,5‘-ADP at 2.0 Å Resolution Reveals the Details of the Ribonucleolytic Active Site,

Autori
Mohan, C. Gopi ; Boix, Ester ; Evans, Hazel R. ; Nikolovski, Zoran ; Nogués, M. Victòria ; Cuchillo, Claudi M. ; Acharya, K. Ravi

Izvornik
Biochemistry (0006-2960) 41 (2002), 40; 12100-12106

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Crystal Structure, ECP, 2‘, 5‘-ADP Complex, 2.0 Å Resolution, Ribonucleolytic Active Site

Sažetak
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 Å) 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 P1 site, while His-128 interacts with the purine ring at the B2 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.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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