3T6J

Structure of human DPPIII in complex with the opioid peptide Tynorphin, at 3.0 Angstroms

Summary for 3T6J

• Entry DOI: 10.2210/pdb3t6j/pdb
• Related: 3T6B
• Descriptor: Dipeptidyl peptidase 3, Tynorphin (3 entities in total)
• Functional Keywords: human dipeptidylpeptidase iii, entropy binding, opioid peptide complex, domain motion, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9NY33
• Total number of polymer chains: 2
• Total formula weight: 82269.56

Authors

Bezerra, G.A.,Gruber, K. (deposition date: 2011-07-28, release date: 2012-04-04, Last modification date: 2023-11-01)

Primary citation

Bezerra, G.A.,Dobrovetsky, E.,Viertlmayr, R.,Dong, A.,Binter, A.,Abramic, M.,Macheroux, P.,Dhe-Paganon, S.,Gruber, K.
Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III.
Proc.Natl.Acad.Sci.USA, 109:6525-6530, 2012

PubMed Abstract: 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.

PubMed: 22493238
DOI: 10.1073/pnas.1118005109

Experimental method

X-RAY DIFFRACTION (2.976 Å)