[English] 日本語
Yorodumi
- PDB-6ysk: 1-phenylpyrroles and 1-enylpyrrolidines as inhibitors of Notum -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ysk
Title1-phenylpyrroles and 1-enylpyrrolidines as inhibitors of Notum
ComponentsPalmitoleoyl-protein carboxylesterase NOTUM
KeywordsHYDROLASE / Notum inhibitor
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 / negative regulation of canonical Wnt signaling pathway / bone development ...[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 / negative regulation of canonical Wnt signaling pathway / bone development / 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-PJK / Palmitoleoyl-protein carboxylesterase NOTUM
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.21 Å
AuthorsZhao, Y. / Jones, E.Y. / Fish, P.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MR/M000141/1 United Kingdom
Cancer Research UKC375/A17721 United Kingdom
CitationJournal: J.Med.Chem. / Year: 2020
Title: Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity.
Authors: Mahy, W. / Patel, M. / Steadman, D. / Woodward, H.L. / Atkinson, B.N. / Svensson, F. / Willis, N.J. / Flint, A. / Papatheodorou, D. / Zhao, Y. / Vecchia, L. / Ruza, R.R. / Hillier, J. / ...Authors: Mahy, W. / Patel, M. / Steadman, D. / Woodward, H.L. / Atkinson, B.N. / Svensson, F. / Willis, N.J. / Flint, A. / Papatheodorou, D. / Zhao, Y. / Vecchia, L. / Ruza, R.R. / Hillier, J. / Frew, S. / Monaghan, A. / Costa, A. / Bictash, M. / Walter, M.W. / Jones, E.Y. / Fish, P.V.
History
DepositionApr 22, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 16, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 23, 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 / 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)45,04116
Polymers43,5671
Non-polymers1,47415
Water2,216123
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2610 Å2
ΔGint-15 kcal/mol
Surface area15880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.940, 71.900, 78.410
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 / Cell line (production host): HEK293 / 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: isolated from a genetically manipulated source
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, 137 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.: 1 / 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.: 8 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-PJK / (3~{S})-1-[4-chloranyl-3-(trifluoromethyl)phenyl]pyrrolidine-3-carboxylic acid


Mass: 293.669 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H11ClF3NO2 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 123 / 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: 1.94 Å3/Da / Density % sol: 36.57 %
Crystal growTemperature: 300 K / Method: vapor diffusion, sitting drop
Details: 1.5 M Ammonium sulphate 0.1 M Sodium citrate, pH4.2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976 Å
DetectorType: DECTRIS EIGER2 X 500K / Detector: PIXEL / Date: Feb 16, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 1.21→59.94 Å / Num. obs: 103841 / % possible obs: 100 % / Redundancy: 13.1 % / Biso Wilson estimate: 14.65 Å2 / Rpim(I) all: 0.022 / Rrim(I) all: 0.08 / Net I/σ(I): 13.1 / Num. measured all: 1362908
Reflection shell

Diffraction-ID: 1 / % possible all: 100

Resolution (Å)Redundancy (%)Mean I/σ(I) obsNum. measured allNum. unique obsRpim(I) allRrim(I) all
1.21-1.23110.75611151240.9253.113
3.28-60.0112.648.76980855340.0120.045

-
Processing

Software
NameVersionClassification
xia2data scaling
PHENIX1.17.1_3660refinement
PDB_EXTRACT3.25data extraction
xia2data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6R8P

6r8p


Resolution: 1.21→39.7 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 22.22
RfactorNum. reflection% reflection
Rfree0.2098 5035 4.85 %
Rwork0.195 --
obs0.1957 103744 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 200.18 Å2 / Biso mean: 26.6138 Å2 / Biso min: 12.81 Å2
Refinement stepCycle: final / Resolution: 1.21→39.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2876 0 89 123 3088
Biso mean--55.14 33.06 -
Num. residues----360
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
1.21-1.220.35771530.355232733426
1.22-1.240.32811660.335832233389
1.24-1.250.3471540.320832583412
1.25-1.270.30781670.31432733440
1.27-1.290.31381780.298132553433
1.29-1.30.3021930.287932113404
1.3-1.320.2981740.267932393413
1.32-1.340.25771680.255632663434
1.34-1.360.26841930.250232523445
1.36-1.390.25191580.240832453403
1.39-1.410.23451570.237932733430
1.41-1.430.25341650.227632713436
1.43-1.460.25851710.218332843455
1.46-1.490.25311550.210232623417
1.49-1.520.2261500.199132943444
1.52-1.560.21191700.192532683438
1.56-1.60.21121800.181632593439
1.6-1.640.22831690.18232733442
1.64-1.690.20731740.183532673441
1.69-1.750.20631770.180432833460
1.75-1.810.20961520.180632973449
1.81-1.880.20481560.18533033459
1.88-1.970.19621500.185433123462
1.97-2.070.20891660.185533253491
2.07-2.20.1881690.184132883457
2.2-2.370.19811970.185433013498
2.37-2.610.21241630.193833643527
2.61-2.980.19541580.201433613519
2.98-3.760.21731590.18834053564
3.76-39.70.18351930.17735243717
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)
10.894-0.0387-0.38391.56180.33972.5326-0.0759-0.0057-0.07990.11310.03870.05550.31610.03090.02220.1680.00380.01160.1239-0.00440.1636-8.9856-10.88572.4789
21.4699-0.09690.40051.62730.03362.7128-0.01470.0538-0.210.02810.0781-0.0350.30630.1346-0.10540.1558-0.00410.01680.1147-0.0150.1527-5.5257-9.2982-4.2819
31.31020.39990.58542.98021.58452.2640.031-0.04910.02240.1616-0.0198-0.14880.13150.0819-0.05450.1095-0.0092-0.01080.13260.00990.13510.44451.9897-2.0141
43.30451.2953-1.75232.6696-1.77272.16220.0509-0.3598-0.12060.0512-0.1223-0.24810.02680.37710.09280.15470.0082-0.04470.2636-0.01880.226810.67842.47374.2213
50.96520.32690.67181.19990.68341.4643-0.0283-0.0970.12640.0103-0.01090.0563-0.0905-0.06870.06470.1428-0.0032-0.00170.1630.00410.1726-7.282213.6592-4.0056
62.0060.06320.18992.87670.81864.69270.0170.02670.083-0.14360.01540.103-0.04940.0654-0.03230.1478-0.0065-0.03090.14250.02430.2075-11.776516.6454-11.3059
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 88 through 159 )A88 - 159
2X-RAY DIFFRACTION2chain 'A' and (resid 160 through 224 )A160 - 224
3X-RAY DIFFRACTION3chain 'A' and (resid 225 through 286 )A225 - 286
4X-RAY DIFFRACTION4chain 'A' and (resid 287 through 320 )A287 - 320
5X-RAY DIFFRACTION5chain 'A' and (resid 321 through 418 )A321 - 418
6X-RAY DIFFRACTION6chain 'A' and (resid 419 through 453 )A419 - 453

+
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