[English] 日本語
Yorodumi
- PDB-8q17: Identification and optimisation of novel inhibitors of the Polyke... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8q17
TitleIdentification and optimisation of novel inhibitors of the Polyketide synthetase 13 thioesterase domain with antitubercular activity
ComponentsPolyketide synthase Pks13
KeywordsTRANSFERASE / inhibitor complex
Function / homology
Function and homology information


DIM/DIP cell wall layer assembly / fatty acid synthase activity / phosphopantetheine binding / 3-oxoacyl-[acyl-carrier-protein] synthase activity / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / fatty acid biosynthetic process / cytoplasm
Similarity search - Function
: / Thioesterase / Thioesterase domain / Polyketide synthase, C-terminal extension / Ketoacyl-synthetase C-terminal extension / Malonyl-CoA ACP transacylase, ACP-binding / : / Acyl transferase / Acyl transferase domain / Acyl transferase domain in polyketide synthase (PKS) enzymes. ...: / Thioesterase / Thioesterase domain / Polyketide synthase, C-terminal extension / Ketoacyl-synthetase C-terminal extension / Malonyl-CoA ACP transacylase, ACP-binding / : / Acyl transferase / Acyl transferase domain / Acyl transferase domain in polyketide synthase (PKS) enzymes. / Acyl transferase domain superfamily / Acyl transferase/acyl hydrolase/lysophospholipase / Polyketide synthase, phosphopantetheine-binding domain / Phosphopantetheine attachment site / Beta-ketoacyl synthase / Beta-ketoacyl synthase, active site / Ketosynthase family 3 (KS3) active site signature. / Ketosynthase family 3 (KS3) domain profile. / Beta-ketoacyl synthase, N-terminal / Beta-ketoacyl synthase, C-terminal / Polyketide synthase, beta-ketoacyl synthase domain / Beta-ketoacyl synthase, N-terminal domain / Beta-ketoacyl synthase, C-terminal domain / Thiolase-like / Phosphopantetheine attachment site / ACP-like superfamily / Carrier protein (CP) domain profile. / Phosphopantetheine binding ACP domain / Alpha/Beta hydrolase fold
Similarity search - Domain/homology
Chem-2Q5 / Chem-IL8 / Polyketide synthase Pks13
Similarity search - Component
Biological speciesMycobacterium tuberculosis (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.71 Å
AuthorsEadsforth, T.C. / Punekar, A.S. / Green, S.R. / Baragana, B.
Funding support United Kingdom, United States, 2items
OrganizationGrant numberCountry
Wellcome Trust100195/Z/12/Z United Kingdom
Bill & Melinda Gates FoundationOPP1066891 United States
CitationJournal: J.Med.Chem. / Year: 2023
Title: Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity.
Authors: Green, S.R. / Wilson, C. / Eadsforth, T.C. / Punekar, A.S. / Tamaki, F.K. / Wood, G. / Caldwell, N. / Forte, B. / Norcross, N.R. / Kiczun, M. / Post, J.M. / Lopez-Roman, E.M. / Engelhart, C. ...Authors: Green, S.R. / Wilson, C. / Eadsforth, T.C. / Punekar, A.S. / Tamaki, F.K. / Wood, G. / Caldwell, N. / Forte, B. / Norcross, N.R. / Kiczun, M. / Post, J.M. / Lopez-Roman, E.M. / Engelhart, C.A. / Lukac, I. / Zuccotto, F. / Epemolu, O. / Boshoff, H.I.M. / Schnappinger, D. / Walpole, C. / Gilbert, I.H. / Read, K.D. / Wyatt, P.G. / Baragana, B.
History
DepositionJul 30, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 22, 2023Provider: repository / Type: Initial release
Revision 1.1Dec 6, 2023Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Polyketide synthase Pks13
B: Polyketide synthase Pks13
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,34312
Polymers63,5552
Non-polymers1,78810
Water6,125340
1
A: Polyketide synthase Pks13
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,5946
Polymers31,7781
Non-polymers8175
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Polyketide synthase Pks13
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,7496
Polymers31,7781
Non-polymers9715
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)88.450, 109.846, 57.590
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Polyketide synthase Pks13


Mass: 31777.742 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis (bacteria) / Strain: (strain ATCC 25618 / H37Rv) / Gene: pks13, Rv3800c / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: I6X8D2, Transferases; Acyltransferases; Transferring groups other than aminoacyl groups

-
Non-polymers , 5 types, 350 molecules

#2: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-IL8 / ~{N}-[2-[4-(azetidin-1-ylcarbonyl)phenyl]ethyl]-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole-5-carboxamide


Mass: 436.460 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H24N4O5 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-2Q5 / (2R)-2-{[(2R)-2-{[(2S)-2-{[(2R)-2-hydroxypropyl]oxy}propyl]oxy}propyl]oxy}propan-1-ol


Mass: 250.332 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H26O5
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 340 / 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: 2.2 Å3/Da / Density % sol: 44.21 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.1M Tris-HCl pH 8.5, 1.8 M Ammonium sulfate, 3% v/v PPG400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Sep 9, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.709→88.46 Å / Num. obs: 56541 / % possible obs: 92 % / Redundancy: 11.6 % / CC1/2: 0.995 / Net I/σ(I): 12.6
Reflection shellResolution: 1.709→1.77 Å / Num. unique obs: 3520 / CC1/2: 0.764

-
Processing

Software
NameVersionClassification
REFMAC5.8.0158refinement
xia2data reduction
xia2data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.71→88.45 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.944 / SU B: 3.779 / SU ML: 0.114 / Cross valid method: THROUGHOUT / ESU R: 0.131 / ESU R Free: 0.128 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23869 2738 4.9 %RANDOM
Rwork0.19531 ---
obs0.19742 53377 91.28 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 33.171 Å2
Baniso -1Baniso -2Baniso -3
1--0.57 Å20 Å20 Å2
2---0.62 Å20 Å2
3---1.18 Å2
Refinement stepCycle: 1 / Resolution: 1.71→88.45 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4321 0 118 340 4779
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.0194569
X-RAY DIFFRACTIONr_bond_other_d0.0020.024203
X-RAY DIFFRACTIONr_angle_refined_deg1.9731.9856202
X-RAY DIFFRACTIONr_angle_other_deg1.10339699
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2395558
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.53723.288222
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.3715712
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.6081544
X-RAY DIFFRACTIONr_chiral_restr0.120.2657
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0215127
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02963
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.0663.1062223
X-RAY DIFFRACTIONr_mcbond_other3.0643.1042222
X-RAY DIFFRACTIONr_mcangle_it4.2974.6422778
X-RAY DIFFRACTIONr_mcangle_other4.2974.6442779
X-RAY DIFFRACTIONr_scbond_it3.9883.5332346
X-RAY DIFFRACTIONr_scbond_other3.9873.5342347
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.9455.1473419
X-RAY DIFFRACTIONr_long_range_B_refined7.56437.3585190
X-RAY DIFFRACTIONr_long_range_B_other7.56437.3665191
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.71→1.754 Å
RfactorNum. reflection% reflection
Rfree0.343 136 -
Rwork0.314 2397 -
obs--56.25 %

+
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