About: Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses

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About: Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses Goto Sponge NotDistinct Permalink

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

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses
Creator	Lim, Liangzhong Roy, Amrita Song, Jianxing Srivastava, Shagun Shi, Jiahai Gupta, Garvita Kang, Jian
topic	covid:ba817ff6b435579197b0e13495447338a7a0f9a2#this
source	Elsevier; Medline; PMC
abstract	Abstract Coronavirus 3C-like and Flavivirus NS2B-NS3 proteases utilize the chymotrypsin fold to harbor their catalytic machineries but also contain additional domains/co-factors. Over the past decade, we aimed to decipher how the extra domains/co-factors mediate the catalytic machineries of SARS 3C-like, Dengue and Zika NS2B-NS3 proteases by characterizing their folding, structures, dynamics and inhibition with NMR, X-ray crystallography and MD simulations, and the results revealed: 1) the chymotrypsin fold of the SARS 3C-like protease can independently fold, while, by contrast, those of Dengue and Zika proteases lack the intrinsic capacity to fold without co-factors. 2) Mutations on the extra domain of SARS 3C-like protease can transform the active catalytic machinery into the inactive collapsed state by structurally-driven allostery. 3) Amazingly, even without detectable structural changes, mutations on the extra domain are sufficient to either inactivate or enhance the catalytic machinery of SARS 3C-like protease by dynamically-driven allostery. 4) Global networks of correlated motions have been identified: for SARS 3C-like protease, N214A inactivates the catalytic machinery by decoupling the network, while STI/A and STIF/A enhance by altering the patterns of the network. The global networks of Dengue and Zika proteases are coordinated by their NS2B-cofactors. 5) Natural products were identified to allosterically inhibit Zika and Dengue proteases through binding a pocket on the back of the active site. Therefore, by introducing extra domains/cofactors, nature develops diverse strategies to regulate the catalytic machinery embedded on the chymotrypsin fold through folding, structurally- and dynamically-driven allostery, all of which might be exploited to develop antiviral drugs.
has issue date	2019-05-31(xsd:dateTime)
bibo:doi	10.1016/j.pbiomolbio.2018.08.009
bibo:pmid	30217495
has license	els-covid
sha1sum (hex)	ba817ff6b435579197b0e13495447338a7a0f9a2
schema:url	https://doi.org/10.1016/j.pbiomolbio.2018.08.009
resource representing a document's title	Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses
has PubMed Central identifier	PMC7111307
has PubMed identifier	30217495
schema:publication	Progress in Biophysics and Molecular Biology
resource representing a document's body	covid:ba817ff6b435579197b0e13495447338a7a0f9a2#body_text
is http://vocab.deri.ie/void#inDataset of	https://covidontheweb.inria.fr:4443/about/id/http/ns.inria.fr/covid19/ba817ff6b435579197b0e13495447338a7a0f9a2
is schema:about of	named entity 'mutations' named entity 'Mutations' named entity 'antiviral drugs' named entity 'STI' named entity 'machinery' named entity 'Therefore' named entity 'STIF' named entity 'protease' named entity 'DRIVEN' named entity 'DECIPHER' named entity 'NMR' named entity 'NS2B' named entity 'BACK OF' named entity 'MD SIMULATIONS' named entity 'ENHANCE' named entity 'RESULTS' named entity 'DEVELOPS' named entity 'STATE' named entity 'ACTIVE SITE' named entity 'TRANSFORM' named entity 'REVEALED' named entity 'STRUCTURAL' named entity 'CORRELATED' named entity 'DRIVEN' named entity 'MEDIATE' named entity 'BUT' named entity 'LACK' named entity 'HAVE' named entity 'NETWORK' named entity 'CONTAIN' named entity 'DECOUPLING' named entity 'STI' named entity 'BINDING' named entity 'DOMAIN' named entity 'DENGUE' named entity 'EXTRA' named entity 'COFACTORS' named entity 'COLLAPSED' named entity 'INACTIVE' named entity 'PROTEASES' named entity 'DENGUE' named entity 'CHYMOTRYPSIN' named entity 'CHANGES' named entity 'HOW' named entity 'PROTEASE' named entity 'FOLD' named entity 'NS3' named entity 'PROTEASES' named entity 'FOLDING' named entity 'CHYMOTRYPSIN' named entity 'EMBEDDED' named entity 'COORDINATED' named entity 'THEIR' named entity 'SARS' named entity 'TO REGULATE' named entity 'X-RAY CRYSTALLOGRAPHY' named entity 'DIVERSE' named entity 'FLAVIVIRUS' named entity 'MACHINERY' named entity 'SARS' named entity 'IDENTIFIED' named entity 'MIGHT BE' named entity 'DECADE' named entity 'ZIKA' named entity 'ALLOSTERY' named entity 'CATALYTIC' named entity 'INHIBITION' named entity 'ANTIVIRAL DRUGS' named entity 'NATURE' named entity 'PATTERNS' named entity 'NETWORKS' named entity 'ALTERING' named entity 'MOTIONS'

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