About: Dual Modes of Modification of Hepatitis A Virus 3C Protease by a Serine-derived β-Lactone: Selective Crystallization and Formation of a Functional Catalytic Triad in the Active Site

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

About: Dual Modes of Modification of Hepatitis A Virus 3C Protease by a Serine-derived β-Lactone: Selective Crystallization and Formation of a Functional Catalytic Triad in the Active Site Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Dual Modes of Modification of Hepatitis A Virus 3C Protease by a Serine-derived β-Lactone: Selective Crystallization and Formation of a Functional Catalytic Triad in the Active Site
Creator	Yin, Jiang Cherney, Maia James, Michael Vederas, John Bergmann, Ernst Jain, Rajendra Lall, Manjinder
Source	Elsevier; Medline; PMC
abstract	Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine proteases responsible for the processing of the viral polyprotein, a function essential for viral maturation and infectivity. This and its structural similarity to other 3C and 3C-like proteases make it an attractive target for the development of antiviral drugs. Previous solution NMR studies have shown that a Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties indistinguishable from the native enzyme, is irreversibly inactivated by N-benzyloxycarbonyl-l-serine-β-lactone (1a) through alkylation of the sulfur atom at the active site Cys172. However, crystallization of an enzyme–inhibitor adduct from the reaction mixture followed by X-ray structural analysis shows only covalent modification of the ε2-nitrogen of the surface His102 by the β-lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple quantum coherence (HMQC) NMR spectra of the enzyme–inhibitor mixture indicates that dual modes of single covalent modification occur with a ≥3:1 ratio of S-alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes readily, probably due to the interaction between the phenyl ring of the N-benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring protein molecule in the crystal. Furthermore, significant structural changes are observed in the active site of the 3C protease, which lead to the formation of a functional catalytic triad with Asp84 accepting one hydrogen bond from His44. Although the 3C protease modified at Cys172 is catalytically inactive, the singly modified His102 N(ε2)-alkylated protein displays a significant level of enzymatic activity, which can be further modified/inhibited by N-iodoacetyl-valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount of the same β-lactone inhibitor (in solution). The success of soaking IVF into HAV 3C–1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme–inhibitor interactions in the proteolytic active site.
has issue date	2005-12-09(xsd:dateTime)
bibo:doi	10.1016/j.jmb.2005.09.074
bibo:pmid	16288920
has license	no-cc
sha1sum (hex)	2dc623e0fed100b9e166ece1962fd0fb0b5cbeb5
schema:url	https://doi.org/10.1016/j.jmb.2005.09.074
resource representing a document's title	Dual Modes of Modification of Hepatitis A Virus 3C Protease by a Serine-derived β-Lactone: Selective Crystallization and Formation of a Functional Catalytic Triad in the Active Site
has PubMed Central identifier	PMC7118759
has PubMed identifier	16288920
schema:publication	J Mol Biol
resource representing a document's body	covid:2dc623e0fed100b9e166ece1962fd0fb0b5cbeb5#body_text
is schema:about of	named entity 'modified' named entity 'dual' named entity 'level' named entity 'ratio' named entity 'catalytic' named entity 'Modes' named entity 'Catalytic' named entity 'Functional' named entity 'CRYSTALLIZATION' named entity 'CATALYTIC TRIAD' named entity 'HEPATITIS A VIRUS' named entity 'SIGNIFICANT' named entity 'INFECTIVITY' named entity 'S-ALKYLATION' named entity 'COVALENT MODIFICATION' named entity 'MODIFIED' named entity 'DUE TO' named entity 'SINGLE' named entity 'RATIO' named entity 'HEPATITIS A VIRUS' named entity 'CRYSTAL' named entity 'PROTEASES' named entity 'LIKE' named entity 'PROTEIN' named entity 'DEVELOPMENT' named entity 'SOLUTION' named entity 'FOLLOWED BY' named entity 'MOIETY' named entity 'FUNCTION' named entity 'LEVEL' named entity 'PROTEASE' named entity 'ALKYLATION' named entity 'MIXTURE' named entity 'CRYSTALLIZATION' named entity 'STRUCTURAL' named entity 'SIMILARITY' named entity 'NEW' named entity 'NO REACTION' named entity 'INHIBITOR' named entity 'ATTRACTIVE' named entity 'SULFUR ATOM' named entity 'INACTIVATED' named entity 'STUDY' named entity 'ACTIVE SITE' named entity 'FORMATION' named entity 'ACTIVE SITE' named entity 'PROPERTIES' named entity 'DUAL' named entity 'CATALYTIC TRIAD' named entity 'VIRAL MATURATION' named entity 'PREVIOUS' named entity 'X-RAY' named entity 'SELECTIVE' named entity 'PROTEINASE' named entity 'EXAMINATION' named entity 'NEIGHBORING' named entity 'LACTONE' named entity 'MODIFICATION' named entity 'DUAL' named entity 'ITS' named entity 'REACTION' named entity 'FORMATION' named entity 'FUNCTIONAL' named entity 'CBZ' named entity 'INTERACTION' named entity 'PROTEIN ' named entity 'INACTIVE' named entity 'CRYSTALS' named entity 'STRUCTURAL ANALYSIS' named entity 'VARIANT' named entity 'PROCESSING' named entity 'NMR SPECTRA' named entity 'CATALYTIC' named entity 'ENZYME-INHIBITOR' named entity 'LACTONE'

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