[English] 日本語
Yorodumi
- PDB-8pm9: Crystal structure of human wild type transthyretin in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8pm9
TitleCrystal structure of human wild type transthyretin in complex with PITB (Pharmacokinetically Improved TTR Binder)
ComponentsTransthyretin
KeywordsTRANSPORT PROTEIN / Aggregation / Inhibitor / Amyloid
Function / homology
Function and homology information


Defective visual phototransduction due to STRA6 loss of function / negative regulation of glomerular filtration / The canonical retinoid cycle in rods (twilight vision) / hormone binding / purine nucleobase metabolic process / molecular sequestering activity / Non-integrin membrane-ECM interactions / phototransduction, visible light / retinoid metabolic process / Retinoid metabolism and transport ...Defective visual phototransduction due to STRA6 loss of function / negative regulation of glomerular filtration / The canonical retinoid cycle in rods (twilight vision) / hormone binding / purine nucleobase metabolic process / molecular sequestering activity / Non-integrin membrane-ECM interactions / phototransduction, visible light / retinoid metabolic process / Retinoid metabolism and transport / hormone activity / azurophil granule lumen / Amyloid fiber formation / Neutrophil degranulation / protein-containing complex binding / protein-containing complex / extracellular space / extracellular exosome / extracellular region / identical protein binding
Similarity search - Function
Transthyretin, conserved site / Transthyretin signature 2. / Transthyretin, thyroxine binding site / Transthyretin signature 1. / Transthyretin / Transthyretin/hydroxyisourate hydrolase / Transthyretin/hydroxyisourate hydrolase domain / Transthyretin/hydroxyisourate hydrolase domain superfamily / HIUase/Transthyretin family
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.85 Å
AuthorsVarejao, N. / Pinheiro, F. / Pallares, I. / Ventura, S. / Reverter, D.
Funding support Spain, 1items
OrganizationGrant numberCountry
Ministerio de Ciencia e Innovacion (MCIN)PGC2018-098423-B-I00 Spain
CitationJournal: Eur.J.Med.Chem. / Year: 2023
Title: PITB: A high affinity transthyretin aggregation inhibitor with optimal pharmacokinetic properties.
Authors: Pinheiro, F. / Varejao, N. / Sanchez-Morales, A. / Bezerra, F. / Navarro, S. / Velazquez-Campoy, A. / Busque, F. / Almeida, M.R. / Alibes, R. / Reverter, D. / Pallares, I. / Ventura, S.
History
DepositionJun 28, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 8, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transthyretin
B: Transthyretin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,1694
Polymers27,5552
Non-polymers6142
Water79344
1
A: Transthyretin
B: Transthyretin
hetero molecules

A: Transthyretin
B: Transthyretin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,3388
Polymers55,1094
Non-polymers1,2294
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Unit cell
Length a, b, c (Å)43.504, 64.089, 84.780
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21221
Symmetry operation#1: x,y,z
#2: x+1/2,-y,-z+1/2
#3: -x,y,-z
#4: -x+1/2,-y,z+1/2
Components on special symmetry positions
IDModelComponents
11A-201-

ZP2

21B-201-

ZP2

-
Components

#1: Protein Transthyretin / ATTR / Prealbumin / TBPA


Mass: 13777.360 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TTR, PALB / Production host: Escherichia coli (E. coli) / References: UniProt: P02766
#2: Chemical ChemComp-ZP2 / (3-fluoranyl-5-oxidanyl-phenyl)-(3-methoxy-5-nitro-4-oxidanyl-phenyl)methanone / Pharmacokinetically Improved TTR Binder (PITB)


Mass: 307.231 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C14H10FNO6 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 44 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.27 Å3/Da / Density % sol: 45.8 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.1M HEPES pH8, 0.2M CaCl2, 25% PEG 400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALBA / Beamline: XALOC / Wavelength: 0.97926 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Feb 19, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97926 Å / Relative weight: 1
ReflectionResolution: 1.85→43.5 Å / Num. obs: 20915 / % possible obs: 99.9 % / Redundancy: 6.3 % / Biso Wilson estimate: 33.23 Å2 / CC1/2: 0.999 / Net I/σ(I): 14.8
Reflection shellResolution: 1.85→1.89 Å / Num. unique obs: 8398 / CC1/2: 0.692 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX(1.17.1_3660: ???)refinement
XDSdata reduction
Aimless(0.7.7)data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.85→42.39 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.46 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2186 1017 4.87 %
Rwork0.1932 --
obs0.1944 20863 99.78 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.85→42.39 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1792 0 44 44 1880
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0061978
X-RAY DIFFRACTIONf_angle_d0.8432718
X-RAY DIFFRACTIONf_dihedral_angle_d10.321276
X-RAY DIFFRACTIONf_chiral_restr0.064298
X-RAY DIFFRACTIONf_plane_restr0.006354
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.85-1.950.2871550.25282783X-RAY DIFFRACTION100
1.95-2.070.24941500.21852771X-RAY DIFFRACTION100
2.07-2.230.25981560.19332771X-RAY DIFFRACTION100
2.23-2.450.22141220.18692839X-RAY DIFFRACTION100
2.45-2.810.25681590.18532809X-RAY DIFFRACTION100
2.81-3.540.20831280.19082879X-RAY DIFFRACTION100
3.54-42.390.19251470.18962994X-RAY DIFFRACTION99
Refinement TLS params.Method: refined / Origin x: 0.818 Å / Origin y: 16.0407 Å / Origin z: 12.7067 Å
111213212223313233
T0.2143 Å20.0016 Å2-0.0027 Å2-0.2361 Å20.0083 Å2--0.2126 Å2
L0.6132 °2-0.3881 °20.0684 °2-1.4456 °20.3427 °2--1.4836 °2
S-0.0455 Å °-0.1376 Å °-0.0138 Å °0.1509 Å °0.0633 Å °-0.0127 Å °0.0709 Å °0.0275 Å °-0.0142 Å °
Refinement TLS groupSelection details: all

+
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