1S4B

Crystal structure of human thimet oligopeptidase.

1S4B の概要

• エントリーDOI: 10.2210/pdb1s4b/pdb
• 分子名称: Thimet oligopeptidase, ZINC ION (3 entities in total)
• 機能のキーワード: zinc metallopeptidase domain, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P52888
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 77575.37

構造登録者

Ray, K.,Hines, C.S.,Coll-Rodriguez, J.,Rodgers, D.W. (登録日: 2004-01-15, 公開日: 2004-07-20, 最終更新日: 2024-02-14)

主引用文献

Ray, K.,Hines, C.S.,Coll-Rodriguez, J.,Rodgers, D.W.
Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization
J.Biol.Chem., 279:20480-20489, 2004

PubMed Abstract: Thimet oligopeptidase (TOP) is a zinc metallopeptidase that metabolizes a number of bioactive peptides and degrades peptides released by the proteasome, limiting antigenic presentation by MHC class I molecules. We present the crystal structure of human TOP at 2.0-A resolution. The active site is located at the base of a deep channel that runs the length of the elongated molecule, an overall fold first seen in the closely related metallopeptidase neurolysin. Comparison of the two related structures indicates hinge-like flexibility and identifies elements near one end of the channel that adopt different conformations. Relatively few of the sequence differences between TOP and neurolysin map to the proposed substrate-binding site, and four of these variable residues may account for differences in substrate specificity. In addition, a loop segment (residues 599-611) in TOP differs in conformation and degree of order from the corresponding neurolysin loop, suggesting it may also play a role in activity differences. Cysteines thought to mediate covalent oligomerization of rat TOP, which can inactivate the enzyme, are found to be surface-accessible in the human enzyme, and additional cysteines (residues 321,350, and 644) may also mediate multimerization in the human homolog. Disorder in the N terminus of TOP indicates it may be involved in subcellular localization, but a potential nuclear import element is found to be part of a helix and, therefore, unlikely to be involved in transport. A large acidic patch on the surface could potentially mediate a protein-protein interaction, possibly through formation of a covalent linkage.

PubMed: 14998993
DOI: 10.1074/jbc.M400795200

実験手法

X-RAY DIFFRACTION (2 Å)