[English] 日本語
Yorodumi
- PDB-7b3p: Notum complex with ARUK3003775 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7b3p
TitleNotum complex with ARUK3003775
ComponentsPalmitoleoyl-protein carboxylesterase NOTUM
KeywordsHYDROLASE / Notum Inhibitor
Function / homology
Function and homology information


protein-containing complex destabilizing activity / [Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / phospholipase C activity / Release of Hh-Np from the secreting cell / regulation of bone mineralization / negative regulation of Wnt signaling pathway / Post-translational protein phosphorylation / negative regulation of canonical Wnt signaling pathway ...protein-containing complex destabilizing activity / [Wnt protein] O-palmitoleoyl-L-serine hydrolase / protein depalmitoleylation / palmitoleyl hydrolase activity / phospholipase C activity / Release of Hh-Np from the secreting cell / 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-SUQ / Palmitoleoyl-protein carboxylesterase NOTUM
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.28 Å
AuthorsZhao, Y. / Jones, E.Y. / Fish, P.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Virtual Screening Directly Identifies New Fragment-Sized Inhibitors of Carboxylesterase Notum with Nanomolar Activity.
Authors: Steadman, D. / Atkinson, B.N. / Zhao, Y. / Willis, N.J. / Frew, S. / Monaghan, A. / Patel, C. / Armstrong, E. / Costelloe, K. / Magno, L. / Bictash, M. / Jones, E.Y. / Fish, P.V. / Svensson, F.
History
DepositionDec 1, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 8, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 21, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Feb 7, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
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)44,70312
Polymers43,5671
Non-polymers1,13511
Water2,036113
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
  • monomer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2130 Å2
ΔGint-55 kcal/mol
Surface area14670 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.317, 73.002, 77.860
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 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

-
Non-polymers , 5 types, 124 molecules

#2: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


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


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-SUQ / 6-((4-chlorophenyl)thio)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one / 6-(4-chlorophenyl)sulfanyl-2~{H}-[1,2,4]triazolo[4,3-b]pyridazin-3-one


Mass: 278.717 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H7ClN4OS / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 113 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.93 Å3/Da / Density % sol: 36.42 %
Crystal growTemperature: 296 K / Method: evaporation / Details: 1.5 M Ammonium Sulphate 0.1 M Sodium Citrate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 24, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.28→53.25 Å / Num. obs: 87713 / % possible obs: 100 % / Redundancy: 26.1 % / CC1/2: 1 / Net I/σ(I): 21.8
Reflection shellResolution: 1.28→1.3 Å / Num. unique obs: 4329 / CC1/2: 0.813

-
Processing

Software
NameVersionClassification
xia2data scaling
PHENIX1.18.2_3874refinement
PDB_EXTRACT3.27data extraction
xia2data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7ARG

7arg


Resolution: 1.28→46.04 Å / SU ML: 0.11 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 17.88 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1986 4307 4.92 %
Rwork0.1876 83312 -
obs0.1882 87619 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 83.4 Å2 / Biso mean: 22.2427 Å2 / Biso min: 12.19 Å2
Refinement stepCycle: final / Resolution: 1.28→46.04 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2696 0 68 113 2877
Biso mean--33.74 26.66 -
Num. residues----344
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
1.28-1.290.24611470.254326962843
1.29-1.310.23891270.244127542881
1.31-1.330.26621420.240527932935
1.33-1.340.23591420.226727362878
1.34-1.360.2571370.223927242861
1.36-1.380.22461480.209927612909
1.38-1.40.23031300.211227402870
1.4-1.420.21481520.207927672919
1.42-1.440.21971390.19827322871
1.44-1.470.24031370.188327622899
1.47-1.490.16611220.179927952917
1.49-1.520.18611420.175927332875
1.52-1.550.19051490.172727572906
1.55-1.580.19471450.169927382883
1.58-1.610.18281630.164327262889
1.61-1.650.17441580.16927792937
1.65-1.690.18521420.161927662908
1.69-1.740.18031570.165727332890
1.74-1.790.20351340.164927772911
1.79-1.850.17881520.17427762928
1.85-1.910.20991450.176827632908
1.91-1.990.17291530.170927562909
1.99-2.080.1871290.173728102939
2.08-2.190.20991530.177328042957
2.19-2.330.20391460.185727792925
2.33-2.510.18511290.186128252954
2.51-2.760.22421810.194227732954
2.76-3.160.19261360.202628622998
3.16-3.980.19751140.188528943008
3.98-46.040.19271560.194130013157
Refinement TLS params.Method: refined / Origin x: 24.902 Å / Origin y: 71.5952 Å / Origin z: 80.8036 Å
111213212223313233
T0.1244 Å20.0034 Å2-0.0058 Å2-0.137 Å2-0.0125 Å2--0.1287 Å2
L0.7166 °2-0.0867 °2-0.0928 °2-1.1218 °20.1111 °2--0.6783 °2
S-0.0209 Å °0.0065 Å °0.0235 Å °-0.0285 Å °0.0086 Å °-0.0077 Å °-0.0799 Å °-0.0014 Å °0.0118 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA87 - 508
2X-RAY DIFFRACTION1allA601 - 846
3X-RAY DIFFRACTION1allA509 - 511

+
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