[English] 日本語
Yorodumi
- PDB-6ts4: Coagulation factor XI protease domain in complex with active site... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ts4
TitleCoagulation factor XI protease domain in complex with active site inhibitor
ComponentsCoagulation factor XIFactor XI
KeywordsHYDROLASE / S1 protease / serine protease / structure-based drug design / active site directed inhibitor
Function / homology
Function and homology information


coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / plasminogen activation / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / heparin binding / serine-type endopeptidase activity / extracellular space ...coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / plasminogen activation / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / heparin binding / serine-type endopeptidase activity / extracellular space / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane
Similarity search - Function
Apple domain. / Apple domain / APPLE domain / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / 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. ...Apple domain. / Apple domain / APPLE domain / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / 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 / Trypsin-like serine proteases / Thrombin, subunit H / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Chem-J7B / Coagulation factor XI
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.17 Å
AuthorsRenatus, M. / Schiering, N.
CitationJournal: J.Med.Chem. / Year: 2020
Title: Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach.
Authors: Lorthiois, E. / Roache, J. / Barnes-Seeman, D. / Altmann, E. / Hassiepen, U. / Turner, G. / Duvadie, R. / Hornak, V. / Karki, R.G. / Schiering, N. / Weihofen, W.A. / Perruccio, F. / Calhoun, ...Authors: Lorthiois, E. / Roache, J. / Barnes-Seeman, D. / Altmann, E. / Hassiepen, U. / Turner, G. / Duvadie, R. / Hornak, V. / Karki, R.G. / Schiering, N. / Weihofen, W.A. / Perruccio, F. / Calhoun, A. / Fazal, T. / Dedic, D. / Durand, C. / Dussauge, S. / Fettis, K. / Tritsch, F. / Dentel, C. / Druet, A. / Liu, D. / Kirman, L. / Lachal, J. / Namoto, K. / Bevan, D. / Mo, R. / Monnet, G. / Muller, L. / Zessis, R. / Huang, X. / Lindsley, L. / Currie, T. / Chiu, Y.H. / Fridrich, C. / Delgado, P. / Wang, S. / Hollis-Symynkywicz, M. / Berghausen, J. / Williams, E. / Liu, H. / Liang, G. / Kim, H. / Hoffmann, P. / Hein, A. / Ramage, P. / D'Arcy, A. / Harlfinger, S. / Renatus, M. / Ruedisser, S. / Feldman, D. / Elliott, J. / Sedrani, R. / Maibaum, J. / Adams, C.M.
History
DepositionDec 19, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 26, 2020Group: Database references / Derived calculations
Category: citation / citation_author ...citation / citation_author / pdbx_struct_conn_angle / struct_conn
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Coagulation factor XI
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,90311
Polymers26,8401
Non-polymers1,06210
Water5,098283
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, inactive hydrolase due to mutation of active site serine.
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1560 Å2
ΔGint-31 kcal/mol
Surface area11780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.320, 60.800, 66.870
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Coagulation factor XI / Factor XI / FXI / Plasma thromboplastin antecedent / PTA


Mass: 26840.496 Da / Num. of mol.: 1
Mutation: SER A 123 SWS P03951 CYS 500 ENGINEERED MUTATION, ALA A 195 SWS P03951 SER 575 ACTIVE SITE MUTATION
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F11 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P03951, coagulation factor XIa

-
Non-polymers , 5 types, 293 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#3: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE / Dimethyl sulfoxide


Mass: 78.133 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-J7B / 2-[2-[[3-[3-(aminomethyl)phenyl]phenyl]carbonylamino]phenyl]ethanoic acid


Mass: 360.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C22H20N2O3 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 283 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.28 Å3/Da / Density % sol: 46.15 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.2 M Ammonium sulfate, 0.1 M BIS-TRIS pH5.5, 25% w/v Polyethylene glycol 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00002 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Sep 24, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00002 Å / Relative weight: 1
ReflectionResolution: 1.17→66.87 Å / Num. obs: 83163 / % possible obs: 99.6 % / Redundancy: 4.757 % / Biso Wilson estimate: 17.793 Å2 / Rmerge(I) obs: 0.031 / Rrim(I) all: 0.035 / Χ2: 0.991 / Net I/σ(I): 22.02
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRrim(I) all% possible all
1.17-1.24.5280.3673.4760650.41699.9
1.2-1.234.370.3094.0759300.35199.2
1.23-1.274.5740.2535.0957740.28699.8
1.27-1.314.7290.2076.1456180.23399.9
1.31-1.354.6660.1787.2754580.299.9
1.35-1.44.5650.1418.9752650.15999.6
1.4-1.454.5810.11111.2750720.12599.1
1.45-1.514.9320.08914.5149120.199.9
1.51-1.584.9360.07218.0347170.08100
1.58-1.654.9120.05822.3145180.06599.9
1.65-1.744.6220.04826.2343080.05499.7
1.74-1.855.0760.0433.4240740.04499.9
1.85-1.985.1550.03340.3738350.03799.8
1.98-2.145.0660.02945.8435930.03399.6
2.14-2.344.7980.02747.4233000.03199.6
2.34-2.624.6790.02550.1230150.02999.7
2.62-3.025.1710.02455.8926730.02699.3
3.02-3.750.02258.6422430.02598.7
3.7-5.234.5780.02157.8317690.02497.8
5.23-66.875.0270.02460.3610240.02697

-
Processing

Software
NameVersionClassification
BUSTERrefinement
XSCALEVersion January 20. 2009data scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.17→43 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.947 / SU R Cruickshank DPI: 0.038 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.041 / SU Rfree Blow DPI: 0.041 / SU Rfree Cruickshank DPI: 0.039
RfactorNum. reflection% reflectionSelection details
Rfree0.2033 4068 -RANDOM
Rwork0.1871 ---
obs0.1879 83162 99.6 %-
Displacement parametersBiso mean: 17.47 Å2
Baniso -1Baniso -2Baniso -3
1--1.1204 Å20 Å20 Å2
2---1.5676 Å20 Å2
3---2.688 Å2
Refine analyzeLuzzati coordinate error obs: 0.14 Å
Refinement stepCycle: LAST / Resolution: 1.17→43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1874 0 63 283 2220
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0082053HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.042798HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d709SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes349HARMONIC5
X-RAY DIFFRACTIONt_it2053HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion261SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact2050SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion5.05
X-RAY DIFFRACTIONt_other_torsion13.02
LS refinement shellResolution: 1.17→1.2 Å
RfactorNum. reflection% reflection
Rfree0.2223 84 -
Rwork0.1917 --
obs--99.94 %
Refinement TLS params.Origin x: 24.9749 Å / Origin y: -2.147 Å / Origin z: -3.5664 Å
111213212223313233
T-0.0214 Å2-0.003 Å20.007 Å2--0.0282 Å2-0.0066 Å2---0.0377 Å2
L0.4656 °2-0.2623 °20.0101 °2-0.5909 °2-0.0716 °2--0.3986 °2
S-0.0131 Å °0.0226 Å °-0.0608 Å °0.0226 Å °0.0288 Å °0.0299 Å °-0.0608 Å °0.0299 Å °-0.0157 Å °
Refinement TLS groupSelection details: { A|* }

+
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