Activation Route of the Schistosoma mansoni Cathepsin B1 Drug Target: Structural Map with a Glycosaminoglycan Switch

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10289025" target="_blank" >RIV/00216208:11310/14:10289025 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/14:00438380 RIV/61388963:_____/14:00438380

Result on the web

<a href="http://dx.doi.org/10.1016/j.str.2014.09.015" target="_blank" >http://dx.doi.org/10.1016/j.str.2014.09.015</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.str.2014.09.015" target="_blank" >10.1016/j.str.2014.09.015</a>

Result language

angličtina

Original language name

Activation Route of the Schistosoma mansoni Cathepsin B1 Drug Target: Structural Map with a Glycosaminoglycan Switch

Original language description

Cathepsin B1 (SmCB1) is a digestive protease of the parasitic blood fluke Schistosoma mansoni and a drug target for the treatment of schistosomiasis, a disease that afflicts over 200 million people. SmCB1 is synthesized as an inactive zymogen in which the N-terminal propeptide blocks the active site. We investigated the activation of the zymogen by which the propeptide is proteolytically removed and its regulation by sulfated polysaccharides (SPs). We determined crystal structures of three molecular forms of SmCB1 along the activation pathway: the zymogen, an activation intermediate with a partially cleaved propeptide, and the mature enzyme. We demonstrate that SPs are essential for the autocatalytic activation of SmCB1, as they interact with a specific heparin-binding domain in the propeptide. An alternative activation route is mediated by an S. mansoni asparaginyl endopeptidase (legumain) which is downregulated by SPs, indicating that SPs act as a molecular switch between both activa

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Structure

ISSN

0969-2126

e-ISSN

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Volume of the periodical

22

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

1786-1798

UT code for WoS article

000345898700012

EID of the result in the Scopus database

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