[English] 日本語
Yorodumi
- PDB-6t8v: Complement factor B in complex with (S)-5,7-Dimethyl-4-((2-phenyl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6t8v
TitleComplement factor B in complex with (S)-5,7-Dimethyl-4-((2-phenylpiperidin-1-yl)methyl)-1H-indole
ComponentsComplement factor B
KeywordsHYDROLASE / Complement immune / inhibitor
Function / homology
Function and homology information


alternative-complement-pathway C3/C5 convertase / classical-complement-pathway C3/C5 convertase complex / complement binding / Alternative complement activation / Activation of C3 and C5 / complement activation, alternative pathway / complement activation / Regulation of Complement cascade / response to bacterium / blood microparticle ...alternative-complement-pathway C3/C5 convertase / classical-complement-pathway C3/C5 convertase complex / complement binding / Alternative complement activation / Activation of C3 and C5 / complement activation, alternative pathway / complement activation / Regulation of Complement cascade / response to bacterium / blood microparticle / serine-type endopeptidase activity / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Complement factor B / Complement B/C2 / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/SCR/CCP superfamily / Sushi/CCP/SCR domain profile. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. ...Complement factor B / Complement B/C2 / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/SCR/CCP superfamily / Sushi/CCP/SCR domain profile. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan
Similarity search - Domain/homology
Chem-MVK / Complement factor B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.29 Å
AuthorsMainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Wiesmann, C. / Adams, C. / Mainolfi, N. / Liao, S.-M. / Argikar, U.A. ...Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Wiesmann, C. / Adams, C. / Mainolfi, N. / Liao, S.-M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / Ding, J. / April, M. / Forster, C. / Serrano-Wu, M. / Capparelli, M. / Ramqaj, R. / Solovay, C. / Cumin, F. / Smith, T.M. / Ferrara, L. / Lee, W. / Long, D. / Prentiss, M. / De Erkenez, A. / Yang, L. / Fang, L. / Sellner, H. / Sirockin, F. / Valeur, E. / Erbel, P. / Ramage, P. / Gerhartz, B. / Schubart, A. / Flohr, S. / Gradoux, N. / Feifel, R. / Vogg, B. / Wiesmann, C. / Maibaum, J. / Eder, J. / Sedrani, R. / Harrison, R.A. / Mogi, M. / Jaffee, B.D. / Adams, C.M.
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a ...Title: Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases.
Authors: Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Liao, S.M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / ...Authors: Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Liao, S.M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / Ding, J. / April, M. / Forster, C. / Serrano-Wu, M. / Capparelli, M. / Ramqaj, R. / Solovay, C. / Cumin, F. / Smith, T.M. / Ferrara, L. / Lee, W. / Long, D. / Prentiss, M. / De Erkenez, A. / Yang, L. / Liu, F. / Sellner, H. / Sirockin, F. / Valeur, E. / Erbel, P. / Ostermeier, D. / Ramage, P. / Gerhartz, B. / Schubart, A. / Flohr, S. / Gradoux, N. / Feifel, R. / Vogg, B. / Wiesmann, C. / Maibaum, J. / Eder, J. / Sedrani, R. / Harrison, R.A. / Mogi, M. / Jaffee, B.D. / Adams, C.M.
History
DepositionOct 25, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 4, 2020Provider: repository / Type: Initial release
Revision 1.1Jul 1, 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 1.2Jan 24, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z ..._atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_PDB_ins_code / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_symmetry / _pdbx_struct_conn_angle.ptnr3_PDB_ins_code / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_ptnr1_PDB_ins_code / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_symmetry

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
AAA: Complement factor B
BBB: Complement factor B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,24811
Polymers65,9122
Non-polymers1,3369
Water1,964109
1
AAA: Complement factor B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,5104
Polymers32,9561
Non-polymers5553
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
BBB: Complement factor B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7377
Polymers32,9561
Non-polymers7816
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)54.652, 97.487, 61.975
Angle α, β, γ (deg.)90.000, 100.465, 90.000
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain: (Details: Chains A B)

-
Components

#1: Protein Complement factor B / / C3/C5 convertase / Glycine-rich beta glycoprotein / GBG / PBF2 / Properdin factor B


Mass: 32955.883 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CFB, BF, BFD / Production host: Drosophila melanogaster (fruit fly)
References: UniProt: P00751, alternative-complement-pathway C3/C5 convertase
#2: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-MVK / 4-[(2~{S})-1-[(5,7-dimethyl-1~{H}-indol-4-yl)methyl]piperidin-2-yl]benzoic acid


Mass: 362.465 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H26N2O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 109 / 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: 2.46 Å3/Da / Density % sol: 50.06 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / Details: 25% PEG3350, 0.1M HEPES PH 7.5, 5 mM inhibitor

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 18, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.29→60.92 Å / Num. obs: 28558 / % possible obs: 99.1 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.102 / Rrim(I) all: 0.121 / Net I/σ(I): 12.22
Reflection shellResolution: 2.29→2.36 Å / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 4.16 / Num. unique obs: 2476 / Rrim(I) all: 0.45 / % possible all: 98.1

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1DLE

1dle


Resolution: 2.29→48.743 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.891 / SU B: 7.086 / SU ML: 0.172 / Cross valid method: FREE R-VALUE / ESU R: 0.347 / ESU R Free: 0.245
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2539 1428 5.001 %
Rwork0.2023 --
all0.205 --
obs-28552 99.153 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 24.576 Å2
Baniso -1Baniso -2Baniso -3
1--0.018 Å20 Å2-0.072 Å2
2--0.076 Å2-0 Å2
3----0.03 Å2
Refinement stepCycle: LAST / Resolution: 2.29→48.743 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4402 0 81 109 4592
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0124636
X-RAY DIFFRACTIONr_angle_refined_deg1.4971.6636294
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.65571
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.66722.533229
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.52915789
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.5131527
X-RAY DIFFRACTIONr_chiral_restr0.1180.2590
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.023484
X-RAY DIFFRACTIONr_nbd_refined0.2030.21842
X-RAY DIFFRACTIONr_nbtor_refined0.3130.23073
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1380.2157
X-RAY DIFFRACTIONr_metal_ion_refined0.0130.22
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2240.243
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1550.28
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined0.0470.23
X-RAY DIFFRACTIONr_mcbond_it1.9932.3182260
X-RAY DIFFRACTIONr_mcangle_it3.2913.462821
X-RAY DIFFRACTIONr_scbond_it2.862.6052376
X-RAY DIFFRACTIONr_scangle_it4.4323.7693467
X-RAY DIFFRACTIONr_lrange_it6.730.2236621
X-RAY DIFFRACTIONr_ncsr_local_group_10.1080.058353
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.29-2.3490.3371030.2619510.26421010.8580.88497.7630.228
2.349-2.4140.3181020.2519470.25320720.830.88498.890.223
2.414-2.4840.3181000.24718970.2520240.8370.87598.6660.219
2.484-2.560.308960.23718210.2419390.8570.89198.86540.213
2.56-2.6430.3930.22917680.23218660.8560.89699.7320.204
2.643-2.7360.331920.22417490.22918480.8690.90499.62120.206
2.736-2.8390.272870.2116500.21317400.8880.91799.82760.195
2.839-2.9540.285860.21316330.21617200.8880.91699.94190.201
2.954-3.0850.25810.21115550.21316380.8930.91699.87790.2
3.085-3.2350.273790.20414850.20815670.8960.92599.80850.2
3.235-3.4090.233740.20714180.20814950.930.93799.79930.205
3.409-3.6150.253700.2113250.21213980.9280.93799.78540.21
3.615-3.8630.273640.20312160.20713300.9140.94696.24060.198
3.863-4.170.208610.16411520.16612220.950.96199.26350.169
4.17-4.5650.164570.14610840.14711440.9740.97399.73780.155
4.565-5.0980.162510.1519740.15110320.9630.96999.32170.164
5.098-5.8760.233440.1638460.1669000.9360.95598.88890.173
5.876-7.1710.23400.1757410.1777830.9390.95899.74460.188
7.171-10.0340.201300.1825760.1836100.9580.95799.34430.206
10.034-48.7430.296180.2613360.2633640.9370.92397.25270.285

+
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