[English] 日本語
Yorodumi
- PDB-7d5l: Discovery of BMS-986144, a Third Generation, Pan Genotype NS3/4A ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7d5l
TitleDiscovery of BMS-986144, a Third Generation, Pan Genotype NS3/4A Protease Inhibitor for the Treatment of Hepatitis C Virus Infection
ComponentsNS3/4A Protease
KeywordsVIRAL PROTEIN / NS3/4A Protease
Function / homology
Function and homology information


transformation of host cell by virus / host cell membrane / serine-type peptidase activity / virion component / symbiont entry into host cell / virion attachment to host cell / proteolysis / membrane / metal ion binding
Similarity search - Function
Hepatitis C virus, NS3 protease, Peptidase S29 / Hepatitis C virus NS3 protease / Hepacivirus/Pegivirus NS3 protease domain profile. / Peptidase S1, PA clan
Similarity search - Domain/homology
Chem-GXO / NS3 protease
Similarity search - Component
Biological speciesHepacivirus C
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsGhosh, K. / Anumula, R. / Kumar, A.
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery of BMS-986144, a Third-Generation, Pan-Genotype NS3/4A Protease Inhibitor for the Treatment of Hepatitis C Virus Infection.
Authors: Sun, L.Q. / Mull, E. / D'Andrea, S. / Zheng, B. / Hiebert, S. / Gillis, E. / Bowsher, M. / Kandhasamy, S. / Baratam, V.R. / Puttaswamy, S. / Pulicharla, N. / Vishwakrishnan, S. / Reddy, S. / ...Authors: Sun, L.Q. / Mull, E. / D'Andrea, S. / Zheng, B. / Hiebert, S. / Gillis, E. / Bowsher, M. / Kandhasamy, S. / Baratam, V.R. / Puttaswamy, S. / Pulicharla, N. / Vishwakrishnan, S. / Reddy, S. / Trivedi, R. / Sinha, S. / Sivaprasad, S. / Rao, A. / Desai, S. / Ghosh, K. / Anumula, R. / Kumar, A. / Rajamani, R. / Wang, Y.K. / Fang, H. / Mathur, A. / Rampulla, R. / Zvyaga, T.A. / Mosure, K. / Jenkins, S. / Falk, P. / Tagore, D.M. / Chen, C. / Rendunchintala, K. / Loy, J. / Meanwell, N.A. / McPhee, F. / Scola, P.M.
History
DepositionSep 26, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 16, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 23, 2020Group: 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
Revision 1.2Mar 27, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NS3/4A Protease
B: NS3/4A Protease
D: NS3/4A Protease
E: NS3/4A Protease
hetero molecules


Theoretical massNumber of molelcules
Total (without water)96,72312
Polymers93,0454
Non-polymers3,6778
Water3,207178
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)46.526, 61.635, 76.374
Angle α, β, γ (deg.)90.420, 105.120, 93.650
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
NS3/4A Protease


Mass: 23261.316 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Details: BMS-986144, a Third Generation, Pan Genotype NS3/4A Protease Inhibitor
Source: (gene. exp.) Hepacivirus C / Production host: Escherichia coli (E. coli) / References: UniProt: A0A0B4WYC6*PLUS
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#3: Chemical
ChemComp-GXO / [1,1,1-tris(fluoranyl)-2-methyl-propan-2-yl] ~{N}-[(1~{S},4~{R},6~{S},7~{Z},11~{R},13~{R},14~{S},18~{R})-13-ethyl-18-(7-fluoranyl-6-methoxy-isoquinolin-1-yl)oxy-11-methyl-4-[(1-methylcyclopropyl)sulfonylcarbamoyl]-2,15-bis(oxidanylidene)-3,16-diazatricyclo[14.3.0.0^{4,6}]nonadec-7-en-14-yl]carbamate


Mass: 853.920 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C40H51F4N5O9S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 178 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.27 Å3/Da / Density % sol: 45.74 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 50mM Ammonium sulphate, 0.1M MES pH6.0, 20% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Nov 14, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 43830 / % possible obs: 98.2 % / Redundancy: 2.2 % / Biso Wilson estimate: 33.88 Å2 / Rmerge(I) obs: 0.069 / Χ2: 1.046 / Net I/σ(I): 7.2 / Num. measured all: 96616
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsΧ2Diffraction-ID% possible all
2.15-2.232.20.43543861.055197.1
2.23-2.322.20.38943511.065197.4
2.32-2.422.20.31143141.049197.6
2.42-2.552.20.24243831.071197.9
2.55-2.712.20.17343661.049197.9
2.71-2.922.20.11544081.044198.3
2.92-3.212.20.0843591.042198.5
3.21-3.682.20.05144061.025198.7
3.68-4.632.20.03844291.02198.8
4.63-502.20.02944281.04199.5

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
HKL-2000data scaling
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→21.27 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.898 / SU R Cruickshank DPI: 0.227 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.217 / SU Rfree Blow DPI: 0.184 / SU Rfree Cruickshank DPI: 0.19
RfactorNum. reflection% reflectionSelection details
Rfree0.238 2196 5.03 %RANDOM
Rwork0.192 ---
obs0.195 43626 98.2 %-
Displacement parametersBiso max: 130.34 Å2 / Biso mean: 36.83 Å2 / Biso min: 11.83 Å2
Baniso -1Baniso -2Baniso -3
1--10.339 Å24.0438 Å2-8.8607 Å2
2--10.3 Å21.3928 Å2
3---0.0391 Å2
Refine analyzeLuzzati coordinate error obs: 0.28 Å
Refinement stepCycle: final / Resolution: 2.15→21.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5533 0 240 178 5951
Biso mean--29.46 40.39 -
Num. residues----772
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1987SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1062HARMONIC5
X-RAY DIFFRACTIONt_it5885HARMONIC20
X-RAY DIFFRACTIONt_nbd1SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion792SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact6868SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d5885HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg8087HARMONIC21.16
X-RAY DIFFRACTIONt_omega_torsion3.66
X-RAY DIFFRACTIONt_other_torsion15.5
LS refinement shellResolution: 2.15→2.17 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.2963 53 6.07 %
Rwork0.2349 820 -
all0.2385 873 -
obs--96.44 %

+
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