Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10288548" target="_blank" >RIV/00216208:11310/14:10288548 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/14:00437123

Result on the web

<a href="http://emboj.embopress.org/content/33/20/2408" target="_blank" >http://emboj.embopress.org/content/33/20/2408</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embj.201489367" target="_blank" >10.15252/embj.201489367</a>

Result language

angličtina

Original language name

Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures

Original language description

The mechanisms of intramembrane proteases are incompletely understood due to the lack of structural data on substrate complexes. To gain insight into substrate binding by rhomboid proteases, we have synthesised a series of novel peptidyl-chloromethylketone (CMK) inhibitors and analysed their interactions with Escherichia coli rhomboid GlpG enzymologically and structurally. We show that peptidyl-CMKs derived from the natural rhomboid substrate TatA from bacterium Providencia stuartii bind GlpG in a substrate-like manner, and their co-crystal structures with GlpG reveal the S1 to S4 subsites of the protease. The S1 subsite is prominent and merges into the water retention site', suggesting intimate interplay between substrate binding, specificity and catalysis. Unexpectedly, the S4 subsite is plastically formed by residues of the L1 loop, an important but hitherto enigmatic feature of the rhomboid fold. We propose that the homologous region of members of the wider rhomboid-like protein su

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

EB - Genetics and molecular biology

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

EMBO Journal

ISSN

0261-4189

e-ISSN

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Volume of the periodical

33

Issue of the periodical within the volume

20

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

2408-2421

UT code for WoS article

000343922500012

EID of the result in the Scopus database

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