Active site alanine mutations convert deubiquitinases into high-affinity ubiquitinbinding proteins
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F18%3AA1901Z5C" target="_blank" >RIV/61988987:17110/18:A1901Z5C - isvavai.cz</a>
Result on the web
<a href="https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=39&SID=C2ThWyDX6vtBzFEKIZA&page=1&doc=1" target="_blank" >https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=39&SID=C2ThWyDX6vtBzFEKIZA&page=1&doc=1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/embr.201745680" target="_blank" >10.15252/embr.201745680</a>
Alternative languages
Result language
angličtina
Original language name
Active site alanine mutations convert deubiquitinases into high-affinity ubiquitinbinding proteins
Original language description
A common strategy for exploring the biological roles of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild-type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight-binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30-fold higher affinity of Ubp8(C146A) for ubiquitin. We show that an alternative option, substituting the active site cysteine with arginine, can inactivate DUBs while also decreasing the affinity for ubiquitin.
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
30204 - Oncology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
EMBO REP
ISSN
1469-221X
e-ISSN
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Volume of the periodical
19
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
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UT code for WoS article
000446430400008
EID of the result in the Scopus database
2-s2.0-85052479055