Novel Structural Mechanism of Allosteric Regulation of Aspartic Peptidases via an Evolutionarily Conserved Exosite
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00489934" target="_blank" >RIV/61388963:_____/18:00489934 - isvavai.cz</a>
Alternative codes found
RIV/60077344:_____/18:00489934 RIV/00216208:11310/18:10377687
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S2451945618300011?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2451945618300011?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.chembiol.2018.01.001" target="_blank" >10.1016/j.chembiol.2018.01.001</a>
Alternative languages
Result language
angličtina
Original language name
Novel Structural Mechanism of Allosteric Regulation of Aspartic Peptidases via an Evolutionarily Conserved Exosite
Original language description
Pepsin-family aspartic peptidases are biosynthesized as inactive zymogens in which the propeptide blocks the active site until its proteolytic removal upon enzyme activation. Here, we describe a novel dual regulatory function for the propeptide using a set of crystal structures of the parasite cathepsin D IrCD1. In the IrCD1 zymogen, intramolecular autoinhibition by the intact propeptide is mediated by an evolutionarily conserved exosite on the enzyme core. After activation, the mature enzyme employs the same exosite to rebind a small fragment derived from the cleaved propeptide. This fragment functions as an effective natural inhibitor of mature IrCD1 that operates in a pH-dependent manner through a unique allosteric inhibition mechanism. The study uncovers the propeptide-binding exosite as a target for the regulation of pepsin-family aspartic peptidases and defines the structural requirements for exosite inhibition.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Chemical Biology
ISSN
2451-9448
e-ISSN
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Volume of the periodical
25
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
318-329
UT code for WoS article
000427600400012
EID of the result in the Scopus database
2-s2.0-85040963567