[English] 日本語
Yorodumi
- PDB-7eow: High-resolution structure of vWF A1 domain in complex with caplac... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7eow
TitleHigh-resolution structure of vWF A1 domain in complex with caplacizumab, the first nanobody-based medicine
Components
  • caplacizumab
  • von Willebrand factor
KeywordsSTRUCTURAL PROTEIN / vWF / vFW A1 / caplacizumab / nanobody
Function / homology
Function and homology information


Defective VWF binding to collagen type I / Enhanced cleavage of VWF variant by ADAMTS13 / Defective VWF cleavage by ADAMTS13 variant / Defective F8 binding to von Willebrand factor / Enhanced binding of GP1BA variant to VWF multimer:collagen / Defective binding of VWF variant to GPIb:IX:V / Weibel-Palade body / hemostasis / platelet alpha granule / Platelet Adhesion to exposed collagen ...Defective VWF binding to collagen type I / Enhanced cleavage of VWF variant by ADAMTS13 / Defective VWF cleavage by ADAMTS13 variant / Defective F8 binding to von Willebrand factor / Enhanced binding of GP1BA variant to VWF multimer:collagen / Defective binding of VWF variant to GPIb:IX:V / Weibel-Palade body / hemostasis / platelet alpha granule / Platelet Adhesion to exposed collagen / GP1b-IX-V activation signalling / p130Cas linkage to MAPK signaling for integrins / cell-substrate adhesion / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / immunoglobulin binding / GRB2:SOS provides linkage to MAPK signaling for Integrins / positive regulation of intracellular signal transduction / Integrin cell surface interactions / collagen binding / Intrinsic Pathway of Fibrin Clot Formation / Integrin signaling / extracellular matrix / platelet alpha granule lumen / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / platelet activation / response to wounding / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / blood coagulation / Signaling by BRAF and RAF1 fusions / integrin binding / Platelet degranulation / protein-folding chaperone binding / protease binding / : / cell adhesion / endoplasmic reticulum / extracellular space / extracellular exosome / extracellular region / identical protein binding
Similarity search - Function
von Willebrand factor, VWA N-terminal domain / Von Willebrand factor / VWA N-terminal / Von Willebrand factor-like domain / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain ...von Willebrand factor, VWA N-terminal domain / Von Willebrand factor / VWA N-terminal / Von Willebrand factor-like domain / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain / VWFD domain profile. / von Willebrand factor (vWF) type D domain / C-terminal cystine knot signature. / von Willebrand factor (vWF) type C domain / Trypsin Inhibitor-like, cysteine rich domain / Serine protease inhibitor-like superfamily / Trypsin Inhibitor like cysteine rich domain / C-terminal cystine knot domain profile. / von Willebrand factor type C domain / Cystine knot, C-terminal / C-terminal cystine knot-like domain (CTCK) / VWFC domain signature. / VWFC domain profile. / von Willebrand factor (vWF) type C domain / VWFC domain / 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 / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
von Willebrand factor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsLee, H.T. / Heo, Y.-S.
CitationJournal: Biochem.Biophys.Res.Commun. / Year: 2021
Title: High-resolution structure of the vWF A1 domain in complex with caplacizumab, the first nanobody-based medicine for treating acquired TTP.
Authors: Lee, H.T. / Park, U.B. / Jeong, T.J. / Gu, N. / Lee, S.H. / Kim, Y. / Heo, Y.S.
History
DepositionApr 23, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 7, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: 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
Revision 1.2Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: von Willebrand factor
B: caplacizumab


Theoretical massNumber of molelcules
Total (without water)41,5672
Polymers41,5672
Non-polymers00
Water6,846380
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, size exclusion chromatography
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1240 Å2
ΔGint-3 kcal/mol
Surface area14740 Å2
Unit cell
Length a, b, c (Å)74.741, 74.741, 122.288
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61
Space group name HallP61
Symmetry operation#1: x,y,z
#2: x-y,x,z+1/6
#3: y,-x+y,z+5/6
#4: -y,x-y,z+1/3
#5: -x+y,-x,z+2/3
#6: -x,-y,z+1/2

-
Components

#1: Protein von Willebrand factor / vWF


Mass: 26508.443 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VWF, F8VWF / Production host: Escherichia coli (E. coli) / References: UniProt: P04275
#2: Antibody caplacizumab


Mass: 15058.780 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 380 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.37 Å3/Da / Density % sol: 48.15 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 20 mM Tris-HCl pH 8 150 mM NaCl 10% glycerol 40% glycerol ethoxylate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PAL/PLS / Beamline: 5C (4A) / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Nov 3, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.6→27.55 Å / Num. obs: 48735 / % possible obs: 95.37 % / Redundancy: 5 % / Biso Wilson estimate: 20.22 Å2 / CC1/2: 0.996 / CC star: 0.999 / Rrim(I) all: 0.064 / Χ2: 1.539 / Net I/σ(I): 5.36
Reflection shellResolution: 1.6→1.63 Å / Redundancy: 10.5 % / Mean I/σ(I) obs: 5.36 / Num. unique obs: 2549 / CC1/2: 0.943 / CC star: 0.985 / Rrim(I) all: 0.541 / Χ2: 0.473

-
Processing

Software
NameVersionClassification
MxDCdata collection
PHENIX1.15.2_3472refinement
HKL-2000data scaling
PHENIXmodel building
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5GGS

5ggs


Resolution: 1.6→27.55 Å / SU ML: 0.1542 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 18.3908
RfactorNum. reflection% reflectionSelection details
Rfree0.1984 2373 4.87 %4.87%
Rwork0.1754 46362 --
obs0.1765 48735 95.37 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 29.81 Å2
Refinement stepCycle: LAST / Resolution: 1.6→27.55 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2600 0 0 380 2980
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00592648
X-RAY DIFFRACTIONf_angle_d0.80073573
X-RAY DIFFRACTIONf_chiral_restr0.0517394
X-RAY DIFFRACTIONf_plane_restr0.0049463
X-RAY DIFFRACTIONf_dihedral_angle_d3.00791617
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.6-1.630.21271780.1882773X-RAY DIFFRACTION98.53
1.63-1.670.21011460.18182847X-RAY DIFFRACTION99.73
1.67-1.70.2141510.1842841X-RAY DIFFRACTION99.57
1.7-1.750.23751370.18872852X-RAY DIFFRACTION99.63
1.75-1.790.22331400.18472833X-RAY DIFFRACTION99.87
1.79-1.850.18611330.18142849X-RAY DIFFRACTION99.8
1.85-1.910.21761110.20352105X-RAY DIFFRACTION73.5
1.91-1.980.35751220.31562459X-RAY DIFFRACTION87.11
1.98-2.050.19941470.17872859X-RAY DIFFRACTION99.9
2.05-2.150.22061300.17782868X-RAY DIFFRACTION100
2.15-2.260.20981340.21172231X-RAY DIFFRACTION78.62
2.26-2.40.21490.18292712X-RAY DIFFRACTION95.4
2.4-2.590.20991520.17812846X-RAY DIFFRACTION99.97
2.59-2.850.20561460.17932848X-RAY DIFFRACTION100
2.85-3.260.19251460.16682898X-RAY DIFFRACTION100
3.26-4.10.16881340.15762611X-RAY DIFFRACTION91.53
4.1-27.550.15651170.14272930X-RAY DIFFRACTION99.58
Refinement TLS params.

Method: refined / 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)
11.63212438186-2.232544643530.3150226050812.32047413559-1.03299795550.797205185793-0.292743433176-0.3317465011960.07974179743960.3939907898470.243839610075-0.0764552845374-0.11343379616-0.0896694373110.001002221362660.3106866174570.0632438266422-0.07609816076270.2053469901190.02110864843110.243204861879-0.68237523221351.447360046765.3547968997
22.07271812927-1.19407382192-0.3395746690012.33828313424-0.08885434744851.18573382682-0.568690947182-0.799152224245-0.4035121802860.7528208885010.5325451506590.103607005674-0.056682307822-0.147831414746-0.1291273776790.4522195517110.148516033059-0.03981989477990.3193549231340.08355438416660.244035913949-0.12006248185146.060596530673.4119984981
30.57174186293-0.4432328974260.442008632032.315523409-0.7714918673591.87833694915-0.0540009465093-0.448957403944-0.536671044204-0.1172474043830.2059047630970.3599555956830.0869252979999-0.306730484369-0.1178757982870.2676358527640.0112306758892-0.03469173728510.1680705323440.0485770367640.3582591788260.41145775201335.031880395461.9088460878
41.64207155176-0.3911913205580.4088176041391.89827029903-0.2705396458391.12086287905-0.141256142635-0.023179530272-0.030435598117-0.03716976266650.0298943830835-0.419570349402-0.030801122880.229017775510.2057713859850.2877797902860.0174294821825-0.06194489327430.2331223862910.03649415511280.40321729391913.352911089239.257227760563.2857773134
52.48426228024-0.8590814645070.1351568751582.41206999117-0.3048639121561.44847154774-0.2519429947110.190463596847-0.0550765550099-0.3322911265150.0522198320805-0.246094968821-0.01400034359530.170799906650.1819106180250.271736620625-0.0092180643407-0.01720378960550.1870603202220.03989790650730.25533602963410.387057982539.452756660257.7546134396
64.35724924904-0.496656090596-0.02806117772953.292007760070.179593021394.94168206822-0.5152616457711.195980487530.331090576751-0.74543937322-0.0465458181301-0.289410477778-0.05253974152130.7708597745190.2305269963930.344064499117-0.06088921832610.06241176483810.3956396924170.09323565019860.33009960880416.951499162841.877979698654.3255437059
72.24176969351-0.733435667553-0.6472606951492.16360973592-1.182029049471.1792240183-0.5238053399470.6166488446680.227531534189-0.656212917590.282590019862-0.239925973595-0.3381316014190.1571367968310.2804651490590.320732671546-0.0948760067907-0.06773261807630.3363048292670.06470911375320.3869712701711.511360478649.307025563154.417714658
83.277091693620.1799527453421.984158844254.577800596940.9047846800434.32628957831-0.4914389044180.3183464630430.455515136551-0.46919393840.0704957061959-0.0449323777345-0.569734564770.3476655054320.3712119578480.314785074271-0.0121540584441-0.07985493936690.1912448593980.05658539457610.3601615683012.9858673087455.67913476856.2110044585
93.11613113784-1.578951742820.5948636819582.76793845601-1.206311127422.485370207840.07242936976040.245878814674-0.1994607718580.0287050796454-0.08110503758690.507574828231-0.0359227863029-0.219085029749-0.009150269696090.132229193421-0.01169802578620.02078091676010.1616635231160.01830485500430.10283119912-32.034097425270.708231833150.4057494188
101.50446904052-1.333668376690.3169040555842.47070518751-0.1456012526060.483943497305-0.385556693085-0.318615618289-0.14476913020.567042903510.4891308075970.01018592355270.129289694232-0.0964884500084-0.09803944370560.2340910265080.01819565067510.03192645820650.1568049058330.0255505758410.128694283476-28.592546800168.048413471954.9405609986
113.700217386971.16323444209-0.3371799795812.01555494522-0.2804516983692.33612760686-0.147250150241-0.0422226168846-0.493215193840.0111772195740.1180632742680.007416402108160.5918276165720.283746264433-0.1086642106170.2815145174490.005514228578040.008170864958810.1231239653150.01883820201730.228552852174-17.94378223956.534119096454.3857402805
122.506174680250.4384518485030.6797983818090.7156640632241.359078597513.04862992097-0.02778197654060.226053370395-0.0393535002559-0.117768901571-0.0210888475226-0.00305170523272-0.29928386867-0.1182865408510.03286217057270.1694882141830.01676770924760.01297456667290.1294201633320.01312185124850.119113265671-23.667438309472.221048192643.0124654693
131.63586981139-0.6023881939170.06901113193272.230734406520.3247904894050.6079984067620.02413989822960.0004877319891870.1933744908130.1841099200940.0385779332425-0.363408388215-0.05557026268830.164549585606-0.04323354733720.158108505319-0.000445266947719-0.01219305681480.130479184282-0.0005289932619980.153459535143-14.145263871472.375986693553.3473634057
142.10654492915-1.714001949010.7176151489273.636332949860.006141834226791.82847753278-0.0844591122816-0.004324414654180.34705282792-0.08650460700970.021427746809-0.263696827769-0.266024489252-0.02956206711960.0744466464890.227612532431-0.00512352868305-0.02459808550.1209511401160.01131732203720.167199978823-20.886056124177.73876653852.5668015871
152.42587666332-1.304504245390.7850707135654.94901118196-1.411394189911.58213095648-0.0605287451711-0.334263230775-0.2911284798790.2484782633350.2153721610660.4269469632120.244653181068-0.278425976296-0.1886332979990.247825305329-0.004695217529740.02838802645470.1427328007990.02482617781750.118262060856-24.658006047168.036786614458.2247536761
161.87944141521-1.32390152633-0.2536040555581.592233037320.08020181014050.33603957638-0.01639162584830.1538319570840.1584827024580.141196549507-0.0347617494653-0.161070486601-0.1556772144790.01330737296990.03224785069760.2216833962280.00726165045646-0.003608590002910.1661724172260.03244980463250.114671748257-27.981961028576.462532393546.0622661805
170.989126833619-0.6183834056430.9973167933374.06504008291-1.450516146852.351371179990.01526330551080.1083572477220.183137517658-0.119273283885-0.113881183696-0.6795422534940.1197780590680.2444147836830.09571257741270.1840126170810.01694837873730.01404904803760.188744848561-0.004502343188320.234855375514-9.5570257131363.729282064948.079092134
183.354969717750.685068301644-0.4959667725382.653685727240.1280123824041.68543101468-0.1653358943560.0977862081375-0.397453305172-0.08272147715560.0603979222654-0.416466556210.3503564021280.2252855714960.0661931720860.182650235486-0.002893737311740.001713851008930.1556168476630.0179176689360.149510076303-18.00080163463.02047528743.1836177231
193.50470175513-2.8986587707-0.05072011453968.402985464730.7330572247712.53186718407-0.04519806884950.174733900731-0.2055906870440.201800182123-0.04360647050950.90998167468-0.195957056112-0.356166017263-0.008710603208950.1652961764820.008876573613450.001771329880980.2319623370420.03904016862060.143901913711-34.941299029574.548592850745.4437269369
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 27 through 86 )
2X-RAY DIFFRACTION2chain 'A' and (resid 87 through 120 )
3X-RAY DIFFRACTION3chain 'A' and (resid 121 through 141 )
4X-RAY DIFFRACTION4chain 'A' and (resid 142 through 160 )
5X-RAY DIFFRACTION5chain 'A' and (resid 161 through 185 )
6X-RAY DIFFRACTION6chain 'A' and (resid 186 through 195 )
7X-RAY DIFFRACTION7chain 'A' and (resid 196 through 206 )
8X-RAY DIFFRACTION8chain 'A' and (resid 207 through 228 )
9X-RAY DIFFRACTION9chain 'B' and (resid 2 through 18 )
10X-RAY DIFFRACTION10chain 'B' and (resid 19 through 26 )
11X-RAY DIFFRACTION11chain 'B' and (resid 27 through 34 )
12X-RAY DIFFRACTION12chain 'B' and (resid 35 through 52 )
13X-RAY DIFFRACTION13chain 'B' and (resid 53 through 62 )
14X-RAY DIFFRACTION14chain 'B' and (resid 63 through 74 )
15X-RAY DIFFRACTION15chain 'B' and (resid 75 through 84 )
16X-RAY DIFFRACTION16chain 'B' and (resid 85 through 100 )
17X-RAY DIFFRACTION17chain 'B' and (resid 101 through 112 )
18X-RAY DIFFRACTION18chain 'B' and (resid 113 through 119 )
19X-RAY DIFFRACTION19chain 'B' and (resid 120 through 129 )

+
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