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Title: Room-temperature neutron and X-ray data collection of 3CL M pro from SARS-CoV-2

Abstract

The replication of SARS-CoV-2 produces two large polyproteins, pp1a and pp1ab, that are inactive until cleavage by the viral chymotrypsin-like cysteine protease enzyme (3CL M pro ) into a series of smaller functional proteins. At the heart of 3CL M pro is an unusual catalytic dyad formed by the side chains of His41 and Cys145 and a coordinated water molecule. The catalytic mechanism by which the enzyme operates is still unknown, as crucial information on the protonation states within the active site is unclear. To experimentally determine the protonation states of the catalytic site and of the other residues in the substrate-binding cavity, and to visualize the hydrogen-bonding networks throughout the enzyme, room-temperature neutron and X-ray data were collected from a large H/D-exchanged crystal of ligand-free (apo) 3CL M pro .

Authors:
ORCiD logo; ; ORCiD logo; ORCiD logo
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1660485
Alternate Identifier(s):
OSTI ID: 1669761
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Published Article
Journal Name:
Acta Crystallographica. Section F, Structural Biology Communications
Additional Journal Information:
Journal Name: Acta Crystallographica. Section F, Structural Biology Communications Journal Volume: 76 Journal Issue: 10; Journal ID: ISSN 2053-230X
Publisher:
International Union of Crystallography
Country of Publication:
United Kingdom
Language:
English
Subject:
Neutron diffraction; X-ray diffraction; SARS-CoV-2; 3CL Mpro

Citation Formats

Kneller, Daniel W., Phillips, Gwyndalyn, Kovalevsky, Andrey, and Coates, Leighton. Room-temperature neutron and X-ray data collection of 3CL M pro from SARS-CoV-2. United Kingdom: N. p., 2020. Web. doi:10.1107/S2053230X20011814.
Kneller, Daniel W., Phillips, Gwyndalyn, Kovalevsky, Andrey, & Coates, Leighton. Room-temperature neutron and X-ray data collection of 3CL M pro from SARS-CoV-2. United Kingdom. doi:10.1107/S2053230X20011814.
Kneller, Daniel W., Phillips, Gwyndalyn, Kovalevsky, Andrey, and Coates, Leighton. Tue . "Room-temperature neutron and X-ray data collection of 3CL M pro from SARS-CoV-2". United Kingdom. doi:10.1107/S2053230X20011814.
@article{osti_1660485,
title = {Room-temperature neutron and X-ray data collection of 3CL M pro from SARS-CoV-2},
author = {Kneller, Daniel W. and Phillips, Gwyndalyn and Kovalevsky, Andrey and Coates, Leighton},
abstractNote = {The replication of SARS-CoV-2 produces two large polyproteins, pp1a and pp1ab, that are inactive until cleavage by the viral chymotrypsin-like cysteine protease enzyme (3CL M pro ) into a series of smaller functional proteins. At the heart of 3CL M pro is an unusual catalytic dyad formed by the side chains of His41 and Cys145 and a coordinated water molecule. The catalytic mechanism by which the enzyme operates is still unknown, as crucial information on the protonation states within the active site is unclear. To experimentally determine the protonation states of the catalytic site and of the other residues in the substrate-binding cavity, and to visualize the hydrogen-bonding networks throughout the enzyme, room-temperature neutron and X-ray data were collected from a large H/D-exchanged crystal of ligand-free (apo) 3CL M pro .},
doi = {10.1107/S2053230X20011814},
journal = {Acta Crystallographica. Section F, Structural Biology Communications},
issn = {2053-230X},
number = 10,
volume = 76,
place = {United Kingdom},
year = {2020},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1107/S2053230X20011814

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