3FVY

Crystal structure of human Dipeptidyl Peptidase III

3FVY の概要

• エントリーDOI: 10.2210/pdb3fvy/pdb
• 分子名称: Dipeptidyl-peptidase 3, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: sgc, dpp3, dipeptidyl peptidase iii, aminopeptidase, hydrolase, metal-binding, metalloprotease, phosphoprotein, protease, structural genomics, structural genomics consortium
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9NY33
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 81923.39

構造登録者

Dong, A.,Dobrovetsky, E.,Seitova, A.,Duncan, B.,Crombet, L.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bochkarev, A.,Cossar, D.,Structural Genomics Consortium (SGC) (登録日: 2009-01-16, 公開日: 2009-02-03, 最終更新日: 2023-09-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)