7PCK

CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K

7PCK の概要

• エントリーDOI: 10.2210/pdb7pck/pdb
• 分子名称: PROTEIN (PROCATHEPSIN K) (1 entity in total)
• 機能のキーワード: hydrolase (thiol protease), procathepsin k, cysteine proteases, proregion, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141431.59

構造登録者

Sivaraman, J.,Lalumiere, M.,Menard, R.,Cygler, M. (登録日: 1998-10-21, 公開日: 1999-10-25, 最終更新日: 2024-11-20)

主引用文献

Sivaraman, J.,Lalumiere, M.,Menard, R.,Cygler, M.
Crystal structure of wild-type human procathepsin K.
Protein Sci., 8:283-290, 1999

PubMed Abstract: Cathepsin K is a lysosomal cysteine protease belonging to the papain superfamily. It has been implicated as a major mediator of osteoclastic bone resorption. Wild-type human procathepsin K has been crystallized in a glycosylated and a deglycosylated form. The latter crystals diffract better, to 3.2 A resolution, and contain four molecules in the asymmetric unit. The structure was solved by molecular replacement and refined to an R-factor of 0.194. The N-terminal fragment of the proregion forms a globular domain while the C-terminal segment is extended and shows substantial flexibility. The proregion interacts with the enzyme along the substrate binding groove and along the proregion binding loop (residues Ser138-Asn156). It binds to the active site in the opposite direction to that of natural substrates. The overall binding mode of the proregion to cathepsin K is similar to that observed in cathepsin L, caricain, and cathepsin B, but there are local differences that likely contribute to the specificity of these proregions for their cognate enzymes. The main observed difference is in the position of the short helix alpha3p (67p-75p), which occupies the S' subsites. As in the other proenzymes, the proregion utilizes the S2 subsite for anchoring by placing a leucine side chain there, according to the specificity of cathepsin K toward its substrate.

PubMed: 10048321

実験手法

X-RAY DIFFRACTION (3.2 Å)