About: Papain‐like protease (PL(pro)) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS‐CoV). PL(pro) also shows significant in vitro deubiquitinating and de‐ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS‐CoV PL(pro) C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 Å resolution. The Ub core makes mostly hydrophilic interactions with PL(pro), while the Leu‐Arg‐Gly‐Gly C‐terminus of Ub is located in the catalytic cleft of PL(pro), mimicking the P4–P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C‐terminal Gly residue of Ub is located in the oxyanion hole consisting of the main‐chain amides of residues 112 and 113. Mutations of residues in the PL(pro)–Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N‐cyclohexyl‐2‐aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PL(pro) inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PL(pro) catalysis.

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Papain‐like protease (PL(pro)) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS‐CoV). PL(pro) also shows significant in vitro deubiquitinating and de‐ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS‐CoV PL(pro) C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 Å resolution. The Ub core makes mostly hydrophilic interactions with PL(pro), while the Leu‐Arg‐Gly‐Gly C‐terminus of Ub is located in the catalytic cleft of PL(pro), mimicking the P4–P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C‐terminal Gly residue of Ub is located in the oxyanion hole consisting of the main‐chain amides of residues 112 and 113. Mutations of residues in the PL(pro)–Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N‐cyclohexyl‐2‐aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PL(pro) inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PL(pro) catalysis. Goto Sponge NotDistinct Permalink

An Entity of Type : fabio:Abstract, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	abstract
value	Papain‐like protease (PL(pro)) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS‐CoV). PL(pro) also shows significant in vitro deubiquitinating and de‐ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS‐CoV PL(pro) C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 Å resolution. The Ub core makes mostly hydrophilic interactions with PL(pro), while the Leu‐Arg‐Gly‐Gly C‐terminus of Ub is located in the catalytic cleft of PL(pro), mimicking the P4–P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C‐terminal Gly residue of Ub is located in the oxyanion hole consisting of the main‐chain amides of residues 112 and 113. Mutations of residues in the PL(pro)–Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N‐cyclohexyl‐2‐aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PL(pro) inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PL(pro) catalysis.
part of	Structural basis for catalysis and ubiquitin recognition by the Severe acute respiratory syndrome coronavirus papain‐like protease
is abstract of	Structural basis for catalysis and ubiquitin recognition by the Severe acute respiratory syndrome coronavirus papain‐like protease

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software