Naslov
Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III

Autori
Bezerra, Gustavo A. ; Dobrovetsky, Elena ; Viertlmayr, Roland ; Dong, Aiping ; Binter, Alexandra ; Abramić, Marija ; Macheroux, Peter ; Dhe-Paganon, Sirano ; Gruber, Karl

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 109 (2012), 17; 6525-6530

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

Ključne riječi
isothermal titration calorimetry; metallopeptidase; peptide binding; X-ray crystallography

Sažetak
Opioid peptides are involved in various essential physiological processes, most notably nociception. Dipeptidyl peptidase III (DPP III) is one of the most important enkephalin-degrading enzymes associated with the mammalian pain modulatory system. Here we describe the X-ray structures of human DPP III and its complex with the opioid peptide tynorphin, which rationalize the enzyme’s substrate specificity and reveal an exceptionally large domain motion upon ligand binding. Microcalorimetric analyses point at an entropy-dominated process, with the release of water molecules from the binding cleft (“entropy reservoir”) as the major thermodynamic driving force. Our results provide the basis for the design of specific inhibitors that enable the elucidation of the exact role of DPP III and the exploration of its potential as a target of pain intervention strategies.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA