6CZK

Crystal structure of wild-type human pro-cathepsin H

Summary for 6CZK

• Entry DOI: 10.2210/pdb6czk/pdb
• Descriptor: Pro-cathepsin H, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: papain family cysteine peptidase, protein degradation in lysosome, inhibitory prodomain, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 39445.32

Authors

Huang, X.,Hao, Y. (deposition date: 2018-04-09, release date: 2018-08-08, Last modification date: 2023-10-04)

Primary citation

Hao, Y.,Purtha, W.,Cortesio, C.,Rui, H.,Gu, Y.,Chen, H.,Sickmier, E.A.,Manzanillo, P.,Huang, X.
Crystal structures of human procathepsin H.
PLoS ONE, 13:e0200374-e0200374, 2018

PubMed Abstract: Cathepsin H is a member of the papain superfamily of lysosomal cysteine proteases. It is the only known aminopeptidase in the family and is reported to be involved in cancer and other major diseases. Like many other proteases, it is synthesized as an inactive proenzyme. Although the crystal structure of mature porcine cathepsin H revealed the binding of the mini-chain and provided structural basis for the aminopeptidase activity, detailed structural and functional information on the inhibition and activation of procathepsin H has been elusive. Here we present the crystal structures of human procathepsin H at 2.00 Å and 1.66 Å resolution. These structures allow us to explore in detail the molecular basis for the inhibition of the mature domain by the prodomain. Comparison with cathepsin H structure reveals how mini-chain reorients upon activation. We further demonstrate that procathepsin H is not auto-activated but can be trans-activated by cathepsin L.

PubMed: 30044821
DOI: 10.1371/journal.pone.0200374

Experimental method

X-RAY DIFFRACTION (2.001 Å)