[English] 日本語
Yorodumi
- PDB-9c7w: human OC43 Main Protease (1-303) in complex with potent inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9c7w
Titlehuman OC43 Main Protease (1-303) in complex with potent inhibitor
ComponentsORF1ab polyprotein
KeywordsVIRAL PROTEIN / main protease / hydrolase / OC43 / protease / peptidase
Function / homology
Function and homology information


: / host cell membrane / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / symbiont-mediated degradation of host mRNA / symbiont-mediated suppression of host ISG15-protein conjugation / omega peptidase activity / endonuclease activity / symbiont-mediated perturbation of host ubiquitin-like protein modification / symbiont-mediated suppression of host NF-kappaB cascade ...: / host cell membrane / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / symbiont-mediated degradation of host mRNA / symbiont-mediated suppression of host ISG15-protein conjugation / omega peptidase activity / endonuclease activity / symbiont-mediated perturbation of host ubiquitin-like protein modification / symbiont-mediated suppression of host NF-kappaB cascade / methyltransferase cap1 activity / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / single-stranded RNA binding / RNA helicase activity / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / viral translational frameshifting / symbiont-mediated activation of host autophagy / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / proteolysis / zinc ion binding / ATP binding / membrane
Similarity search - Function
RNA-dependent RNA polymerase, coronavirus HKU1-like / Coronavirus Nsp3 DPUP domain / Peptidase C30/C16, Betacoronavirus / Betacoronavirus, lineage A, NSP1 / NSP3, DPUP domain, murine hepatitis virus-like / Non-structural protein 2, MHV-like / Peptidase C16 family / Betacoronavirus, lineage A, NSP1 / DNA2/NAM7-like helicase / AAA domain ...RNA-dependent RNA polymerase, coronavirus HKU1-like / Coronavirus Nsp3 DPUP domain / Peptidase C30/C16, Betacoronavirus / Betacoronavirus, lineage A, NSP1 / NSP3, DPUP domain, murine hepatitis virus-like / Non-structural protein 2, MHV-like / Peptidase C16 family / Betacoronavirus, lineage A, NSP1 / DNA2/NAM7-like helicase / AAA domain / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / NSP14, guanine-N7-methyltransferase domain, coronavirus / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / NSP12 RNA-dependent RNA polymerase, coronavirus / : / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Coronavirus Nsp12 Interface domain profile. / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / Nidovirus 2-O-methyltransferase / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Non-structural protein NSP15, N-terminal domain superfamily, coronavirus / Non-structural protein NSP15, middle domain superfamily / Coronavirus replicase NSP15, N-terminal oligomerization / Nonstructural protein 15, middle domain, coronavirus / Nonstructural protein 13, 1B domain, coronavirus / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Nidovirus 3'-5' exoribonuclease domain / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Non-structural protein NSP16, coronavirus-like / Non-structural protein 14, coronavirus / RNA polymerase, N-terminal, coronavirus / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) domain profile. / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Endoribonuclease EndoU-like / NendoU domain, nidovirus / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / DNA2/NAM7 helicase-like, C-terminal / AAA domain / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / NSP1, C-terminal domain, betacoronavirus / : / Betacoronavirus (BetaCoV) Nsp1 C-terminal domain profile. / Betacoronavirus Nsp3e group 2-specific marker (G2M) domain profile. / Betacoronavirus Nsp3c-C domain profile. / Betacoronavirus Nsp3e nucleic acid-binding (NAB) domain profile. / DPUP/SUD, C-terminal, betacoronavirus / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Non-structural protein NSP3A domain-like superfamily / Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus / Non-structural protein 6, betacoronavirus / Betacoronavirus nucleic acid-binding (NAB) / Papain-like viral protease, palm and finger domains, coronavirus / Papain-like protease, N-terminal domain superfamily, coronavirus / : / Coronavirus (CoV) Nsp2 middle domain profile. / NSP1, globular domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp1 globular domain profile. / Coronavirus (CoV) Nsp2 N-terminal domain profile. / Coronavirus (CoV) Nsp2 C-terminal domain profile. / Nonstructural protein 2, N-terminal domain, coronavirus / Non-structural protein 2, C-terminal domain, coronavirus / NSP3, second ubiquitin-like (Ubl) domain, coronavirus / Coronavirus Nsp3a Ubl domain profile. / Coronavirus Nsp3d Ubl domain profile. / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / Peptidase family C16 domain profile. / : / : / Coronavirus replicase NSP7 / Coronavirus 3Ecto domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp7 cofactor domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp8 cofactor domain profile. / Coronavirus Nsp9 single-stranded RNA (ssRNA)-binding domain profile. / Coronavirus (CoV) ExoN/MTase coactivator domain profile. / Coronavirus (CoV) Nsp3 Y domain profile. / Coronavirus Nsp4 C-terminal (Nsp4C) domain profile. / Coronavirus main protease (M-pro) domain profile. / Peptidase C30, coronavirus / Peptidase C16, coronavirus / Non-structural protein NSP9, coronavirus / Non-structural protein NSP7, coronavirus / Non-structural protein NSP8, coronavirus
Similarity search - Domain/homology
: / ORF1ab polyprotein
Similarity search - Component
Biological speciesHuman coronavirus OC43
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.08 Å
AuthorsTang, J.Y. / Knapp, M.S.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2024
Title: Identification of Potent, Broad-Spectrum Coronavirus Main Protease Inhibitors for Pandemic Preparedness.
Authors: Barkan, D.T. / Garland, K. / Zhang, L. / Eastman, R.T. / Hesse, M. / Knapp, M. / Ornelas, E. / Tang, J. / Cortopassi, W.A. / Wang, Y. / King, F. / Jia, W. / Nguyen, Z. / Frank, A.O. / Chan, ...Authors: Barkan, D.T. / Garland, K. / Zhang, L. / Eastman, R.T. / Hesse, M. / Knapp, M. / Ornelas, E. / Tang, J. / Cortopassi, W.A. / Wang, Y. / King, F. / Jia, W. / Nguyen, Z. / Frank, A.O. / Chan, R. / Fang, E. / Fuller, D. / Busby, S. / Carias, H. / Donahue, K. / Tandeske, L. / Diagana, T.T. / Jarrousse, N. / Moser, H. / Sarko, C. / Dovala, D. / Moquin, S. / Marx, V.M.
History
DepositionJun 11, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ORF1ab polyprotein
B: ORF1ab polyprotein
C: ORF1ab polyprotein
D: ORF1ab polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)133,1128
Polymers131,8514
Non-polymers1,2614
Water11,926662
1
A: ORF1ab polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2782
Polymers32,9631
Non-polymers3151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: ORF1ab polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2782
Polymers32,9631
Non-polymers3151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: ORF1ab polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2782
Polymers32,9631
Non-polymers3151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: ORF1ab polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2782
Polymers32,9631
Non-polymers3151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)67.245, 129.805, 140.074
Angle α, β, γ (deg.)90, 90, 90
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein
ORF1ab polyprotein


Mass: 32962.727 Da / Num. of mol.: 4 / Mutation: P3460L
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human coronavirus OC43 / Gene: Pp1ab
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: U3M6R3
#2: Chemical
ChemComp-A1AUY / (8S)-3-(4,4-difluorocyclohexyl)-5-(pyrimidin-2-yl)pyrazolo[1,5-a]pyrimidine


Mass: 315.321 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C16H15F2N5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 662 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.32 Å3/Da / Density % sol: 46.94 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1M HEPES pH 7.5, 8% EG, 10% PEG 8K

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 2.0.1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 5, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.08→95.21 Å / Num. obs: 73340 / % possible obs: 98.6 % / Redundancy: 5.5 % / CC1/2: 0.985 / Rmerge(I) obs: 0.12 / Rpim(I) all: 0.056 / Rrim(I) all: 0.133 / Net I/σ(I): 7
Reflection shellResolution: 2.08→2.087 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.895 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 2188 / CC1/2: 0.291 / Rpim(I) all: 0.58 / % possible all: 84.2

-
Processing

Software
NameVersionClassification
BUSTER2.11.8refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.08→70.04 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.927 / SU R Cruickshank DPI: 0.245 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.258 / SU Rfree Blow DPI: 0.192 / SU Rfree Cruickshank DPI: 0.189
RfactorNum. reflection% reflectionSelection details
Rfree0.2459 3582 -RANDOM
Rwork0.2142 ---
obs0.2158 72700 97.7 %-
Displacement parametersBiso mean: 39.09 Å2
Baniso -1Baniso -2Baniso -3
1--2.4119 Å20 Å20 Å2
2--0.6091 Å20 Å2
3---1.8028 Å2
Refine analyzeLuzzati coordinate error obs: 0.28 Å
Refinement stepCycle: LAST / Resolution: 2.08→70.04 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9070 0 92 662 9824
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0089506HARMONIC2
X-RAY DIFFRACTIONt_angle_deg113017HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3119SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes1598HARMONIC5
X-RAY DIFFRACTIONt_it9450HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion1242SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies10HARMONIC1
X-RAY DIFFRACTIONt_ideal_dist_contact8972SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.76
X-RAY DIFFRACTIONt_other_torsion14.77
LS refinement shellResolution: 2.08→2.1 Å
RfactorNum. reflection% reflection
Rfree0.3188 91 -
Rwork0.3118 --
obs0.3123 1454 80.93 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.140.22610.23390.42610.07081.0666-0.04180.04790.11080.0479-0.0417-0.06310.1108-0.06310.0834-0.0512-0.00410.0124-0.0253-0.02410.0502-13.6429-14.245433.3079
20.50580.4398-0.54220.477-0.27670.95330.09120.0706-0.16080.0706-0.08870.0366-0.16080.0366-0.0025-0.0201-0.0596-0.0182-0.01780.00180.0155-20.6392-48.362534.1037
30.2207-0.1527-0.40041.2884-0.29570.693-0.025-0.14180.0371-0.1418-0.02360.00650.03710.00650.0486-0.05780.01270.0013-0.0866-0.02290.0867-0.62741.484716.923
40.32910.15580.4251.083-0.02490.7171-0.02240.1076-0.0510.1076-0.0209-0.0296-0.051-0.02960.0433-0.04170.0008-0.0228-0.0746-0.00810.0658-34.0407-0.370851.3923
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A1 - 298
2X-RAY DIFFRACTION1{ A|* }A301
3X-RAY DIFFRACTION2{ B|* }B1 - 298
4X-RAY DIFFRACTION2{ B|* }B301
5X-RAY DIFFRACTION3{ C|* }C1 - 298
6X-RAY DIFFRACTION3{ C|* }C301
7X-RAY DIFFRACTION4{ D|* }D1 - 298
8X-RAY DIFFRACTION4{ D|* }D301

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more