data_50262
#######################
# Entry information #
#######################
save_entry_information
_Saveframe_category entry_information
_Entry_title
;
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication
;
_BMRB_accession_number 50262
_BMRB_flat_file_name bmr50262.str
_Entry_type original
_Submission_date 2020-05-06
_Accession_date 2020-05-06
_Entry_origination author
_NMR_STAR_version 2.1.1
_Experimental_method NMR
_Details
;
Time domain data for experiments along with spectrometer parameters.
Chemical shift assignments found in journal article of the same same name:
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.
Contains NMR data of inhibitor preparation as well as protease-inhibitor binding studies.
These data are available from the time-domain data directory for this entry.
http://www.bmrb.wisc.edu/ftp/pub/bmrb/timedomain/bmr50262/
;
loop_
_Author_ordinal
_Author_family_name
_Author_given_name
_Author_middle_initials
_Author_family_title
1 Vuong Wayne . .
2 McKay Ryan . .
3 Vederas John . .
stop_
loop_
_Saveframe_category_type
_Saveframe_category_type_count
assigned_chemical_shifts 3
stop_
loop_
_Data_type
_Data_type_count
"1H chemical shifts" 3
"13C chemical shifts" 3
stop_
loop_
_Revision_date
_Revision_keyword
_Revision_author
_Revision_detail
2020-10-16 update BMRB 'update entry citation'
2020-06-30 update Author 'add chemical shifts'
2020-06-08 original Author 'original release'
stop_
_Original_release_date 2020-05-06
save_
#############################
# Citation for this entry #
#############################
save_citations_1
_Saveframe_category entry_citation
_Citation_full .
_Citation_title
;
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication
;
_Citation_status published
_Citation_type journal
_CAS_abstract_code .
_MEDLINE_UI_code .
_PubMed_ID 32855413
loop_
_Author_ordinal
_Author_family_name
_Author_given_name
_Author_middle_initials
_Author_family_title
1 Vuong Wayne . .
2 Khan 'M. Bashir' . .
3 Fischer Conrad . .
4 Arutyunova Elena . .
5 Lamer Tess . .
6 Shields Justin . .
7 Saffran Holly A. .
8 McKay Ryan T. .
9 'van Belkum' Marco J. .
10 Joyce Michael . .
11 Young Howard S. .
12 Tyrrell 'D. Lorne' . .
13 Vederas John C. .
14 Lemieux 'M. Joanne' . .
stop_
_Journal_abbreviation 'Nat. Commun.'
_Journal_name_full 'Nature communications'
_Journal_volume 11
_Journal_issue 1
_Journal_ISSN 2041-1723
_Journal_CSD .
_Book_chapter_title .
_Book_volume .
_Book_series .
_Book_ISBN .
_Conference_state_province .
_Conference_abstract_number .
_Page_first 4282
_Page_last 4282
_Year 2020
_Details .
loop_
_Keyword
'COVID-19, SARS-CoV-2, Mpro, 3CLpro, coronavirus, main protease, SARS'
stop_
save_
##################################
# Molecular system description #
##################################
save_assembly_1
_Saveframe_category molecular_system
_Mol_system_name 'Protease-Inhibitor Complex'
_Enzyme_commission_number .
loop_
_Mol_system_component_name
_Mol_label
'Inhibitor (GC373) bound' $GC373
'Inhibitor (GC373) free form 1' $GC373
'Inhibitor (GC373) free form 2' $GC373
'SARS-CoV-2 Mpro' $Mpro
stop_
_System_molecular_weight .
_System_physical_state native
_System_oligomer_state ?
_System_paramagnetic no
_System_thiol_state 'disulfide and other bound'
loop_
_Biological_function
'Inhibition of SARS-CoV-2 polyprotein (pp1a, pp1ab) processing'
stop_
_Database_query_date .
_Details
;
Protease-Inhibitor Complex;
The inhibitor GC373 has formula: C21H29N3O5, MS: 403.48.
There is a single covalent bond between: Inhibitor (GC373) and residue 145 Cys (atom SG).
NMR data contains precursors/intermediates in the synthesis of this compound.
Enzyme binding experiments performed using a C13-labelled version of GC373 with label at aldehyde carbon.
;
save_
########################
# Monomeric polymers #
########################
save_Mpro
_Saveframe_category monomeric_polymer
_Mol_type polymer
_Mol_polymer_class protein
_Name_common 'SARS-CoV-2 main protease'
_Molecular_mass .
_Mol_thiol_state 'disulfide and other bound'
loop_
_Biological_function
'SARS-CoV-2 main protease (Mpro)'
stop_
_Details .
##############################
# Polymer residue sequence #
##############################
_Residue_count 306
_Mol_residue_sequence
;
SGFRKMAFPSGKVEGCMVQV
TCGTTTLNGLWLDDVVYCPR
HVICTSEDMLNPNYEDLLIR
KSNHNFLVQAGNVQLRVIGH
SMQNCVLKLKVDTANPKTPK
YKFVRIQPGQTFSVLACYNG
SPSGVYQCAMRPNFTIKGSF
LNGSCGSVGFNIDYDCVSFC
YMHHMELPTGVHAGTDLEGN
FYGPFVDRQTAQAAGTDTTI
TVNVLAWLYAAVINGDRWFL
NRFTTTLNDFNLVAMKYNYE
PLTQDHVDILGPLSAQTGIA
VLDMCASLKELLQNGMNGRT
ILGSALLEDEFTPFDVVRQC
SGVTFQ
;
loop_
_Residue_seq_code
_Residue_author_seq_code
_Residue_label
1 1 SER 2 2 GLY 3 3 PHE 4 4 ARG 5 5 LYS
6 6 MET 7 7 ALA 8 8 PHE 9 9 PRO 10 10 SER
11 11 GLY 12 12 LYS 13 13 VAL 14 14 GLU 15 15 GLY
16 16 CYS 17 17 MET 18 18 VAL 19 19 GLN 20 20 VAL
21 21 THR 22 22 CYS 23 23 GLY 24 24 THR 25 25 THR
26 26 THR 27 27 LEU 28 28 ASN 29 29 GLY 30 30 LEU
31 31 TRP 32 32 LEU 33 33 ASP 34 34 ASP 35 35 VAL
36 36 VAL 37 37 TYR 38 38 CYS 39 39 PRO 40 40 ARG
41 41 HIS 42 42 VAL 43 43 ILE 44 44 CYS 45 45 THR
46 46 SER 47 47 GLU 48 48 ASP 49 49 MET 50 50 LEU
51 51 ASN 52 52 PRO 53 53 ASN 54 54 TYR 55 55 GLU
56 56 ASP 57 57 LEU 58 58 LEU 59 59 ILE 60 60 ARG
61 61 LYS 62 62 SER 63 63 ASN 64 64 HIS 65 65 ASN
66 66 PHE 67 67 LEU 68 68 VAL 69 69 GLN 70 70 ALA
71 71 GLY 72 72 ASN 73 73 VAL 74 74 GLN 75 75 LEU
76 76 ARG 77 77 VAL 78 78 ILE 79 79 GLY 80 80 HIS
81 81 SER 82 82 MET 83 83 GLN 84 84 ASN 85 85 CYS
86 86 VAL 87 87 LEU 88 88 LYS 89 89 LEU 90 90 LYS
91 91 VAL 92 92 ASP 93 93 THR 94 94 ALA 95 95 ASN
96 96 PRO 97 97 LYS 98 98 THR 99 99 PRO 100 100 LYS
101 101 TYR 102 102 LYS 103 103 PHE 104 104 VAL 105 105 ARG
106 106 ILE 107 107 GLN 108 108 PRO 109 109 GLY 110 110 GLN
111 111 THR 112 112 PHE 113 113 SER 114 114 VAL 115 115 LEU
116 116 ALA 117 117 CYS 118 118 TYR 119 119 ASN 120 120 GLY
121 121 SER 122 122 PRO 123 123 SER 124 124 GLY 125 125 VAL
126 126 TYR 127 127 GLN 128 128 CYS 129 129 ALA 130 130 MET
131 131 ARG 132 132 PRO 133 133 ASN 134 134 PHE 135 135 THR
136 136 ILE 137 137 LYS 138 138 GLY 139 139 SER 140 140 PHE
141 141 LEU 142 142 ASN 143 143 GLY 144 144 SER 145 145 CYS
146 146 GLY 147 147 SER 148 148 VAL 149 149 GLY 150 150 PHE
151 151 ASN 152 152 ILE 153 153 ASP 154 154 TYR 155 155 ASP
156 156 CYS 157 157 VAL 158 158 SER 159 159 PHE 160 160 CYS
161 161 TYR 162 162 MET 163 163 HIS 164 164 HIS 165 165 MET
166 166 GLU 167 167 LEU 168 168 PRO 169 169 THR 170 170 GLY
171 171 VAL 172 172 HIS 173 173 ALA 174 174 GLY 175 175 THR
176 176 ASP 177 177 LEU 178 178 GLU 179 179 GLY 180 180 ASN
181 181 PHE 182 182 TYR 183 183 GLY 184 184 PRO 185 185 PHE
186 186 VAL 187 187 ASP 188 188 ARG 189 189 GLN 190 190 THR
191 191 ALA 192 192 GLN 193 193 ALA 194 194 ALA 195 195 GLY
196 196 THR 197 197 ASP 198 198 THR 199 199 THR 200 200 ILE
201 201 THR 202 202 VAL 203 203 ASN 204 204 VAL 205 205 LEU
206 206 ALA 207 207 TRP 208 208 LEU 209 209 TYR 210 210 ALA
211 211 ALA 212 212 VAL 213 213 ILE 214 214 ASN 215 215 GLY
216 216 ASP 217 217 ARG 218 218 TRP 219 219 PHE 220 220 LEU
221 221 ASN 222 222 ARG 223 223 PHE 224 224 THR 225 225 THR
226 226 THR 227 227 LEU 228 228 ASN 229 229 ASP 230 230 PHE
231 231 ASN 232 232 LEU 233 233 VAL 234 234 ALA 235 235 MET
236 236 LYS 237 237 TYR 238 238 ASN 239 239 TYR 240 240 GLU
241 241 PRO 242 242 LEU 243 243 THR 244 244 GLN 245 245 ASP
246 246 HIS 247 247 VAL 248 248 ASP 249 249 ILE 250 250 LEU
251 251 GLY 252 252 PRO 253 253 LEU 254 254 SER 255 255 ALA
256 256 GLN 257 257 THR 258 258 GLY 259 259 ILE 260 260 ALA
261 261 VAL 262 262 LEU 263 263 ASP 264 264 MET 265 265 CYS
266 266 ALA 267 267 SER 268 268 LEU 269 269 LYS 270 270 GLU
271 271 LEU 272 272 LEU 273 273 GLN 274 274 ASN 275 275 GLY
276 276 MET 277 277 ASN 278 278 GLY 279 279 ARG 280 280 THR
281 281 ILE 282 282 LEU 283 283 GLY 284 284 SER 285 285 ALA
286 286 LEU 287 287 LEU 288 288 GLU 289 289 ASP 290 290 GLU
291 291 PHE 292 292 THR 293 293 PRO 294 294 PHE 295 295 ASP
296 296 VAL 297 297 VAL 298 298 ARG 299 299 GLN 300 300 CYS
301 301 SER 302 302 GLY 303 303 VAL 304 304 THR 305 305 PHE
306 306 GLN
stop_
_Sequence_homology_query_date .
_Sequence_homology_query_revised_last_date .
save_
#############
# Ligands #
#############
save_UED
_Saveframe_category ligand
_Mol_type "non-polymer (NON-POLYMER)"
_Name_common N~2~-[(benzyloxy)carbonyl]-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide
_BMRB_code UED
_PDB_code UED
_Molecular_mass 405.488
_Mol_charge 0
_Mol_paramagnetic .
_Mol_aromatic yes
_Details .
loop_
_Atom_name
_PDB_atom_name
_Atom_type
_Atom_chirality
_Atom_charge
_Atom_oxidation_number
_Atom_unpaired_electrons
C7 C7 C . 0 . ?
O8 O8 O . 0 . ?
C9 C9 C . 0 . ?
O10 O10 O . 0 . ?
C1 C1 C . 0 . ?
C2 C2 C . 0 . ?
C3 C3 C . 0 . ?
C4 C4 C . 0 . ?
C5 C5 C . 0 . ?
C6 C6 C . 0 . ?
N11 N11 N . 0 . ?
C12 C12 C . 0 . ?
C17 C17 C . 0 . ?
O18 O18 O . 0 . ?
C13 C13 C . 0 . ?
C14 C14 C . 0 . ?
C15 C15 C . 0 . ?
C16 C16 C . 0 . ?
N19 N19 N . 0 . ?
C20 C20 C . 0 . ?
C21 C21 C . 0 . ?
O22 O22 O . 0 . ?
C24 C24 C . 0 . ?
C25 C25 C . 0 . ?
C26 C26 C . 0 . ?
C27 C27 C . 0 . ?
N28 N28 N . 0 . ?
C29 C29 C . 0 . ?
O30 O30 O . 0 . ?
H1 H1 H . 0 . ?
H2 H2 H . 0 . ?
H3 H3 H . 0 . ?
H4 H4 H . 0 . ?
H5 H5 H . 0 . ?
H6 H6 H . 0 . ?
H7 H7 H . 0 . ?
H8 H8 H . 0 . ?
H9 H9 H . 0 . ?
H10 H10 H . 0 . ?
H11 H11 H . 0 . ?
H12 H12 H . 0 . ?
H13 H13 H . 0 . ?
H14 H14 H . 0 . ?
H15 H15 H . 0 . ?
H16 H16 H . 0 . ?
H17 H17 H . 0 . ?
H18 H18 H . 0 . ?
H19 H19 H . 0 . ?
H20 H20 H . 0 . ?
H21 H21 H . 0 . ?
H22 H22 H . 0 . ?
H23 H23 H . 0 . ?
H24 H24 H . 0 . ?
H25 H25 H . 0 . ?
H26 H26 H . 0 . ?
H27 H27 H . 0 . ?
H28 H28 H . 0 . ?
H29 H29 H . 0 . ?
H30 H30 H . 0 . ?
H31 H31 H . 0 . ?
stop_
loop_
_Bond_order
_Bond_atom_one_atom_name
_Bond_atom_two_atom_name
_PDB_bond_atom_one_atom_name
_PDB_bond_atom_two_atom_name
SING C16 C14 ? ?
DOUB C3 C2 ? ?
SING C3 C4 ? ?
SING C2 C1 ? ?
SING C14 C13 ? ?
SING C14 C15 ? ?
SING C13 C12 ? ?
DOUB C4 C5 ? ?
SING O8 C7 ? ?
SING O8 C9 ? ?
SING N11 C12 ? ?
SING N11 C9 ? ?
SING C1 C7 ? ?
DOUB C1 C6 ? ?
DOUB O18 C17 ? ?
SING C5 C6 ? ?
SING C12 C17 ? ?
DOUB C9 O10 ? ?
SING C17 N19 ? ?
SING C26 C27 ? ?
SING C26 C25 ? ?
SING N19 C20 ? ?
SING C20 C21 ? ?
SING C20 C24 ? ?
SING C27 N28 ? ?
SING O22 C21 ? ?
SING C25 C24 ? ?
SING C25 C29 ? ?
SING N28 C29 ? ?
DOUB C29 O30 ? ?
SING C7 H1 ? ?
SING C7 H2 ? ?
SING C2 H3 ? ?
SING C3 H4 ? ?
SING C4 H5 ? ?
SING C5 H6 ? ?
SING C6 H7 ? ?
SING N11 H8 ? ?
SING C12 H9 ? ?
SING C13 H10 ? ?
SING C13 H11 ? ?
SING C14 H12 ? ?
SING C15 H13 ? ?
SING C15 H14 ? ?
SING C15 H15 ? ?
SING C16 H16 ? ?
SING C16 H17 ? ?
SING C16 H18 ? ?
SING N19 H19 ? ?
SING C20 H20 ? ?
SING C24 H21 ? ?
SING C24 H22 ? ?
SING C25 H23 ? ?
SING C26 H24 ? ?
SING C26 H25 ? ?
SING C27 H26 ? ?
SING C27 H27 ? ?
SING N28 H28 ? ?
SING C21 H29 ? ?
SING C21 H30 ? ?
SING O22 H31 ? ?
stop_
_Mol_thiol_state .
_Sequence_homology_query_date .
save_
####################
# Natural source #
####################
save_natural_source_1
_Saveframe_category natural_source
loop_
_Mol_label
_Organism_name_common
_NCBI_taxonomy_ID
_Superkingdom
_Kingdom
_Genus
_Species
_Strain
_Details
$GC373 . . . . . . . 'Protease inhibitor synthesized by chemical means.'
$Mpro SARS-CoV-2 2697049 Viruses . . . rep,1a-1b .
stop_
save_
#########################
# Experimental source #
#########################
save_experimental_source_1
_Saveframe_category experimental_source
loop_
_Mol_label
_Production_method
_Host_organism_name_common
_Genus
_Species
_Strain
_Vector_name
_Details
$GC373 'chemical synthesis' . . . . . 'Protease inhibitor synthesized by chemical means.'
$Mpro 'recombinant technology' 'Escherichia coli' . . 12009 . .
stop_
save_
#####################################
# Sample contents and methodology #
#####################################
########################
# Sample description #
########################
save_sample_1
_Saveframe_category sample
_Sample_type solution
_Details 'See cited reference experimental section for details.'
loop_
_Mol_label
_Concentration_value
_Concentration_value_units
_Isotopic_labeling
$GC373 0.0995 mM '[U-100% 13C]'
$Mpro 2.6 mg/mL 'natural abundance'
DTT 20 mM 'natural abundance'
'potassium phosphate' 50 mM 'natural abundance'
stop_
save_
############################
# Computer software used #
############################
save_software_1
_Saveframe_category software
_Name VNMRj
_Version '4.2A, patch 110'
loop_
_Task
'data analysis'
'data collection'
stop_
_Details .
save_
#########################
# Experimental detail #
#########################
##################################
# NMR Spectrometer definitions #
##################################
save_NMR_spectrometer_1
_Saveframe_category NMR_spectrometer
_Manufacturer Agilent
_Model VNMRS
_Field_strength 700
_Details '4-channel, inverse cold probe'
save_
#############################
# NMR applied experiments #
#############################
save_2D_1H-13C_HSQC_1
_Saveframe_category NMR_applied_experiment
_Experiment_name '2D 1H-13C HSQC'
_Sample_label $sample_1
save_
#######################
# Sample conditions #
#######################
save_sample_conditions_1
_Saveframe_category sample_conditions
_Details 'Conditions of Enzyme-Inhibitor Binding Assay. See cited reference experimental section for details.'
loop_
_Variable_type
_Variable_value
_Variable_value_error
_Variable_value_units
pH 7.5 . pH
pressure 1 . atm
temperature 300 . K
stop_
save_
####################
# NMR parameters #
####################
##############################
# Assigned chemical shifts #
##############################
################################
# Chemical shift referencing #
################################
save_chem_shift_reference_1
_Saveframe_category chemical_shift_reference
_Details .
loop_
_Mol_common_name
_Atom_type
_Atom_isotope_number
_Atom_group
_Chem_shift_units
_Chem_shift_value
_Reference_method
_Reference_type
_External_reference_sample_geometry
_External_reference_location
_External_reference_axis
_Indirect_shift_ratio
HOD C 13 protons ppm 4.72 internal indirect . . . 0.251449530
HOD H 1 protons ppm 4.72 internal direct . . . 1.0
stop_
save_
###################################
# Assigned chemical shift lists #
###################################
###################################################################
# Chemical Shift Ambiguity Index Value Definitions #
# #
# The values other than 1 are used for those atoms with different #
# chemical shifts that cannot be assigned to stereospecific atoms #
# or to specific residues or chains. #
# #
# Index Value Definition #
# #
# 1 Unique (including isolated methyl protons, #
# geminal atoms, and geminal methyl #
# groups with identical chemical shifts) #
# (e.g. ILE HD11, HD12, HD13 protons) #
# 2 Ambiguity of geminal atoms or geminal methyl #
# proton groups (e.g. ASP HB2 and HB3 #
# protons, LEU CD1 and CD2 carbons, or #
# LEU HD11, HD12, HD13 and HD21, HD22, #
# HD23 methyl protons) #
# 3 Aromatic atoms on opposite sides of #
# symmetrical rings (e.g. TYR HE1 and HE2 #
# protons) #
# 4 Intraresidue ambiguities (e.g. LYS HG and #
# HD protons or TRP HZ2 and HZ3 protons) #
# 5 Interresidue ambiguities (LYS 12 vs. LYS 27) #
# 6 Intermolecular ambiguities (e.g. ASP 31 CA #
# in monomer 1 and ASP 31 CA in monomer 2 #
# of an asymmetrical homodimer, duplex #
# DNA assignments, or other assignments #
# that may apply to atoms in one or more #
# molecule in the molecular assembly) #
# 9 Ambiguous, specific ambiguity not defined #
# #
###################################################################
save_assigned_chemical_shifts_1_1
_Saveframe_category assigned_chemical_shifts
_Details
;
Contains NMR data of inhibitor preparation as well as protease-inhibitor binding studies.
These data are available from the time-domain data directory for this entry.
http://www.bmrb.wisc.edu/ftp/pub/bmrb/timedomain/bmr50262/
;
loop_
_Experiment_label
'2D 1H-13C HSQC'
stop_
loop_
_Sample_label
$sample_1
stop_
_Sample_conditions_label $sample_conditions_1
_Chem_shift_reference_set_label $chem_shift_reference_1
_Mol_system_component_name 'Inhibitor (GC373) bound'
_Text_data_format .
_Text_data .
loop_
_Atom_shift_assign_ID
_Residue_author_seq_code
_Residue_seq_code
_Residue_label
_Atom_name
_Atom_type
_Chem_shift_value
_Chem_shift_value_error
_Chem_shift_ambiguity_code
1 . 1 UED H29 H 5.65 0.02 1
2 . 1 UED C21 C 76.0 0.2 1
stop_
save_
save_assigned_chemical_shifts_1_2
_Saveframe_category assigned_chemical_shifts
_Details
;
Contains NMR data of inhibitor preparation as well as protease-inhibitor binding studies.
These data are available from the time-domain data directory for this entry.
http://www.bmrb.wisc.edu/ftp/pub/bmrb/timedomain/bmr50262/
;
loop_
_Experiment_label
'2D 1H-13C HSQC'
stop_
loop_
_Sample_label
$sample_1
stop_
_Sample_conditions_label $sample_conditions_1
_Chem_shift_reference_set_label $chem_shift_reference_1
_Mol_system_component_name 'Inhibitor (GC373) free form 1'
_Text_data_format .
_Text_data .
loop_
_Atom_shift_assign_ID
_Residue_author_seq_code
_Residue_seq_code
_Residue_label
_Atom_name
_Atom_type
_Chem_shift_value
_Chem_shift_value_error
_Chem_shift_ambiguity_code
1 . 1 UED H29 H 4.82 0.02 6
2 . 1 UED C21 C 90.8 0.2 6
stop_
save_
save_assigned_chemical_shifts_1_3
_Saveframe_category assigned_chemical_shifts
_Details
;
Contains NMR data of inhibitor preparation as well as protease-inhibitor binding studies.
These data are available from the time-domain data directory for this entry.
http://www.bmrb.wisc.edu/ftp/pub/bmrb/timedomain/bmr50262/
;
loop_
_Experiment_label
'2D 1H-13C HSQC'
stop_
loop_
_Sample_label
$sample_1
stop_
_Sample_conditions_label $sample_conditions_1
_Chem_shift_reference_set_label $chem_shift_reference_1
_Mol_system_component_name 'Inhibitor (GC373) free form 2'
_Text_data_format .
_Text_data .
loop_
_Atom_shift_assign_ID
_Residue_author_seq_code
_Residue_seq_code
_Residue_label
_Atom_name
_Atom_type
_Chem_shift_value
_Chem_shift_value_error
_Chem_shift_ambiguity_code
1 . 1 UED H29 H 4.91 0.02 6
2 . 1 UED C21 C 90.2 0.2 6
stop_
save_