5LPF

Kallikrein-related peptidase 10

5LPF の概要

• エントリーDOI: 10.2210/pdb5lpf/pdb
• 分子名称: Kallikrein-10, SULFATE ION (3 entities in total)
• 機能のキーワード: serine protease, zymogen-like enzyme, zn2+ inhibition, tumor suppressor, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : O43240
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52129.49

構造登録者

Goettig, P.,Debela, M.,Magdolen, V.,Bode, W.,Brandstetter, H. (登録日: 2016-08-12, 公開日: 2016-10-05, 最終更新日: 2024-10-23)

主引用文献

Debela, M.,Magdolen, V.,Bode, W.,Brandstetter, H.,Goettig, P.
Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10.
Biol.Chem., 397:1251-1264, 2016

PubMed Abstract: Although kallikrein-related peptidase 10 (KLK10) is expressed in a variety of human tissues and body fluids, knowledge of its physiological functions is fragmentary. Similarly, the pathophysiology of KLK10 in cancer is not well understood. In some cancer types, a role as tumor suppressor has been suggested, while in others elevated expression is associated with poor patient prognosis. Active human KLK10 exhibits a unique, three residue longer N-terminus with respect to other serine proteases and an extended 99-loop nearly as long as in tissue kallikrein KLK1. Crystal structures of recombinant ligand-free KLK10 and a Zn2+ bound form explain to some extent the mixed trypsin- and chymotrypsin-like substrate specificity. Zn2+-inhibition of KLK10 appears to be based on a unique mechanism, which involves direct binding and blocking of the catalytic triad. Since the disordered N-terminus and several loops adopt a zymogen-like conformation, the active protease conformation is very likely induced by interaction with the substrate, in particular at the S1 subsite and at the unusual Ser193 as part of the oxyanion hole. The KLK10 structures indicate that the N-terminus, the nearby 75-, 148-, and the 99-loops are connected in an allosteric network, which is present in other trypsin-like serine proteases with several variations.

PubMed: 27611765
DOI: 10.1515/hsz-2016-0205

実験手法

X-RAY DIFFRACTION (2.7 Å)