[English] 日本語
Yorodumi
- PDB-6t7p: human plasmakallikrein protease domain in complex with active sit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6t7p
Titlehuman plasmakallikrein protease domain in complex with active site directed inhibitor
ComponentsPlasma kallikrein
KeywordsHYDROLASE / S1 protease / serine protease / structure-based drug design / active site directed inhibitor
Function / homology
Function and homology information


plasma kallikrein / Factor XII activation / Defective SERPING1 causes hereditary angioedema / positive regulation of fibrinolysis / zymogen activation / plasminogen activation / Defective factor XII causes hereditary angioedema / Activation of Matrix Metalloproteinases / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation ...plasma kallikrein / Factor XII activation / Defective SERPING1 causes hereditary angioedema / positive regulation of fibrinolysis / zymogen activation / plasminogen activation / Defective factor XII causes hereditary angioedema / Activation of Matrix Metalloproteinases / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / serine-type endopeptidase activity / proteolysis / extracellular space / extracellular exosome / extracellular region / 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 / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family ...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 / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, serine active site. / Serine proteases, trypsin domain profile. / 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
GLUTATHIONE / Chem-MU8 / PHOSPHATE ION / Plasma kallikrein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.416 Å
AuthorsRenatus, M.
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
DepositionOct 22, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 26, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Plasma kallikrein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,92515
Polymers27,1871
Non-polymers1,73814
Water4,810267
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2980 Å2
ΔGint12 kcal/mol
Surface area11640 Å2
MethodPISA
Unit cell
Length a, b, c (Å)57.100, 59.150, 86.720
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 Plasma kallikrein / Fletcher factor / Kininogenin / Plasma prekallikrein / PKK


Mass: 27186.953 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KLKB1, KLK3 / Production host: Escherichia coli BL21 (bacteria) / Variant (production host): DE3 Rosetta / References: UniProt: P03952, plasma kallikrein

-
Non-polymers , 6 types, 281 molecules

#2: Chemical ChemComp-GSH / GLUTATHIONE


Mass: 307.323 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H17N3O6S
#3: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-MU8 / (2~{S},4~{R})-1-[[(3~{S})-3-azanyl-2,3-dihydro-1-benzofuran-6-yl]carbonyl]-~{N}-(3-chlorophenyl)-4-phenyl-pyrrolidine-2-carboxamide


Mass: 461.940 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H24ClN3O3 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 267 / 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: 2.69 Å3/Da / Density % sol: 54.33 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 20% PEG10000, 200 mM Sodium phosphate (monobasic), corresponds to Nextal condition #87 from PEG series

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: May 28, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.416→37.126 Å / Num. obs: 56111 / % possible obs: 99.1 % / Redundancy: 4.3 % / CC1/2: 0.999 / Rmerge(I) obs: 0.049 / Rpim(I) all: 0.027 / Rrim(I) all: 0.057 / Net I/σ(I): 15.4
Reflection shellResolution: 1.416→1.421 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.549 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1920 / CC1/2: 0.847 / Rpim(I) all: 0.417 / Rrim(I) all: 0.639 / % possible all: 93.3

-
Processing

Software
NameVersionClassification
XDSdata reduction
Aimless0.7.4data scaling
PHENIX1.14_3260refinement
PDB_EXTRACT3.25data extraction
MOLREP8.2.01phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2any

2any


Resolution: 1.416→37.126 Å / SU ML: 0.14 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 17.47
RfactorNum. reflection% reflection
Rfree0.1878 2807 5 %
Rwork0.1524 --
obs0.1542 56101 99.05 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 130.47 Å2 / Biso mean: 24.8591 Å2 / Biso min: 4.74 Å2
Refinement stepCycle: final / Resolution: 1.416→37.126 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1877 0 116 268 2261
Biso mean--38.86 35.94 -
Num. residues----237
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.416-1.440.25481340.2166250294
1.4402-1.46640.22981390.2028264299
1.4664-1.49460.28061390.19252643100
1.4946-1.52510.26371390.19882654100
1.5251-1.55830.23621390.19112640100
1.5583-1.59450.21871400.16792677100
1.5945-1.63440.2231430.15812668100
1.6344-1.67860.20921400.14422638100
1.6786-1.7280.18771400.14062677100
1.728-1.78370.16641390.14082654100
1.7837-1.84750.1891400.1407265599
1.8475-1.92150.17571400.1399263999
1.9215-2.00890.17181390.1363264499
2.0089-2.11480.18011410.1353267999
2.1148-2.24730.18321390.1419264299
2.2473-2.42080.16261400.145269099
2.4208-2.66430.19891410.1566269799
2.6643-3.04970.19071430.1645271799
3.0497-3.84170.18631440.1447273799

+
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