[English] 日本語
Yorodumi
- PDB-6zvl: ARUK3000263 complex with Notum -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6zvl
TitleARUK3000263 complex with Notum
ComponentsPalmitoleoyl-protein carboxylesterase NOTUM
KeywordsSIGNALING PROTEIN / Notum / inhibitor / Wnt
Function / homology
Function and homology information


[Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / Release of Hh-Np from the secreting cell / phospholipase C activity / regulation of bone mineralization / negative regulation of Wnt signaling pathway / Post-translational protein phosphorylation / bone development / negative regulation of canonical Wnt signaling pathway ...[Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / Release of Hh-Np from the secreting cell / phospholipase C activity / regulation of bone mineralization / negative regulation of Wnt signaling pathway / Post-translational protein phosphorylation / bone development / negative regulation of canonical Wnt signaling pathway / Wnt signaling pathway / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / endoplasmic reticulum lumen / extracellular region
Similarity search - Function
Pectinacetylesterase/NOTUM / Pectinacetylesterase
Similarity search - Domain/homology
Chem-QR2 / Palmitoleoyl-protein carboxylesterase NOTUM
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.3 Å
AuthorsZhao, Y. / Ruza, R.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Cancer Research UKC375/A17721 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/M000141/1 United Kingdom
CitationJournal: J.Med.Chem. / Year: 2020
Title: 5-Phenyl-1,3,4-oxadiazol-2(3 H )-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit.
Authors: Mahy, W. / Willis, N.J. / Zhao, Y. / Woodward, H.L. / Svensson, F. / Sipthorp, J. / Vecchia, L. / Ruza, R.R. / Hillier, J. / Kjaer, S. / Frew, S. / Monaghan, A. / Bictash, M. / Salinas, P.C. ...Authors: Mahy, W. / Willis, N.J. / Zhao, Y. / Woodward, H.L. / Svensson, F. / Sipthorp, J. / Vecchia, L. / Ruza, R.R. / Hillier, J. / Kjaer, S. / Frew, S. / Monaghan, A. / Bictash, M. / Salinas, P.C. / Whiting, P. / Vincent, J.P. / Jones, E.Y. / Fish, P.V.
History
DepositionJul 24, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 11, 2020Provider: repository / Type: Initial release
Revision 1.1Nov 25, 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 31, 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: Palmitoleoyl-protein carboxylesterase NOTUM
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,65610
Polymers43,5671
Non-polymers1,0889
Water2,162120
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1620 Å2
ΔGint-33 kcal/mol
Surface area15630 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.805, 71.791, 78.036
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein / Sugars , 2 types, 2 molecules A

#1: Protein Palmitoleoyl-protein carboxylesterase NOTUM / hNOTUM


Mass: 43567.148 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NOTUM, OK/SW-CL.30 / Production host: Homo sapiens (human)
References: UniProt: Q6P988, [Wnt protein] O-palmitoleoyl-L-serine hydrolase
#2: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 5 types, 128 molecules

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


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE / Dimethyl sulfoxide


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-QR2 / 5-[4-chloranyl-3-(trifluoromethyl)phenyl]-3~{H}-1,3,4-oxadiazol-2-one


Mass: 264.588 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H4ClF3N2O2 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 120 / 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: 1.92 Å3/Da / Density % sol: 36.02 %
Crystal growTemperature: 293 K / Method: evaporation / pH: 4.2
Details: 1.5 M Ammonium Sulphate 0.1 M Sodium Citrate, pH 4.2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.9159 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: May 2, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9159 Å / Relative weight: 1
ReflectionResolution: 1.3→59.8 Å / Num. obs: 83089 / % possible obs: 99.9 % / Redundancy: 12.3 % / CC1/2: 0.99 / Net I/σ(I): 14.3
Reflection shellResolution: 1.3→1.32 Å / Mean I/σ(I) obs: 1.8 / Num. unique obs: 3974 / CC1/2: 0.6

-
Processing

Software
NameVersionClassification
xia2data scaling
PHENIX1.18.2_3874refinement
PDB_EXTRACT3.25data extraction
xia2data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6TR5

6tr5


Resolution: 1.3→52.83 Å / SU ML: 0.18 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 27.09 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2226 3945 4.82 %
Rwork0.2007 77825 -
obs0.2018 81770 98.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 141.79 Å2 / Biso mean: 24.8594 Å2 / Biso min: 9.17 Å2
Refinement stepCycle: final / Resolution: 1.3→52.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2790 0 95 120 3005
Biso mean--45 30.78 -
Num. residues----348
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 28

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.3-1.320.39171230.38782496261990
1.32-1.330.42991450.38362675282096
1.33-1.350.421450.35532668281395
1.35-1.370.381640.36062672283696
1.37-1.390.40651250.34132698282397
1.39-1.410.38911410.33832714285597
1.41-1.430.35671420.31752727286997
1.43-1.450.33641510.29022728287998
1.45-1.480.29951510.27972714286598
1.48-1.510.30311280.26622766289498
1.51-1.540.28171240.24952796292098
1.54-1.570.29621470.232743289099
1.57-1.60.21621300.23192749287998
1.6-1.640.25251510.22182785293699
1.64-1.680.21741260.21612786291299
1.68-1.720.2411520.20462793294599
1.72-1.780.23811740.197527542928100
1.78-1.830.22421270.19112821294899
1.83-1.90.22121280.18592825295399
1.9-1.970.20811350.177228092944100
1.97-2.060.19441370.169628562993100
2.06-2.170.18121420.169328422984100
2.17-2.310.2091580.171628132971100
2.31-2.490.19531300.173528692999100
2.49-2.740.19811370.182628622999100
2.74-3.130.1771440.181628903034100
3.13-3.950.1921590.182429023061100
3.95-52.830.20751290.189430723201100
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)
11.1274-0.1419-0.46911.1616-0.53513.0162-0.0108-0.00290.1194-0.02530.00190.0257-0.1954-0.0531-0.00920.12960.0049-0.01530.0851-0.02350.140222.201881.728379.0635
21.68930.1388-0.02842.12760.39530.55680.03390.10180.0424-0.114-0.0289-0.1934-0.08610.0351-0.0690.08110.0090.00860.1027-0.00030.108232.594570.460979.1641
35.3254-2.68531.66114.1559-2.65353.433-0.05460.11920.30120.0371-0.0875-0.364-0.19240.22880.13160.1148-0.01790.02570.1491-0.01350.157741.869369.773676.6535
41.23670.1565-0.28931.44970.77891.5824-0.04280.0346-0.10530.0381-0.0060.07310.0782-0.08950.05590.09170.00120.00260.09970.00570.1121.851857.509183.9456
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 86 through 232 )A86 - 232
2X-RAY DIFFRACTION2chain 'A' and (resid 233 through 297 )A233 - 297
3X-RAY DIFFRACTION3chain 'A' and (resid 298 through 320 )A298 - 320
4X-RAY DIFFRACTION4chain 'A' and (resid 321 through 452 )A321 - 452

+
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