[English] 日本語
Yorodumi
- PDB-3kad: Structure-guided design of alpha-amino acid-derived Pin1 inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3kad
TitleStructure-guided design of alpha-amino acid-derived Pin1 inhibitors
ComponentsPeptidyl-prolyl cis-trans isomerase NIMA-interacting 1
KeywordsISOMERASE / SBDD / PPIASE / ROTAMASE / SMALL MOLECULE / Proline directed kinase / cell cycle / Oncogenic transformation / Nucleus / Phosphoprotein
Function / homology
Function and homology information


cis-trans isomerase activity / phosphothreonine residue binding / negative regulation of cell motility / ubiquitin ligase activator activity / regulation of protein localization to nucleus / GTPase activating protein binding / protein targeting to mitochondrion / mitogen-activated protein kinase kinase binding / regulation of mitotic nuclear division / negative regulation of SMAD protein signal transduction ...cis-trans isomerase activity / phosphothreonine residue binding / negative regulation of cell motility / ubiquitin ligase activator activity / regulation of protein localization to nucleus / GTPase activating protein binding / protein targeting to mitochondrion / mitogen-activated protein kinase kinase binding / regulation of mitotic nuclear division / negative regulation of SMAD protein signal transduction / protein peptidyl-prolyl isomerization / PI5P Regulates TP53 Acetylation / negative regulation of amyloid-beta formation / cytoskeletal motor activity / postsynaptic cytosol / phosphoserine residue binding / RHO GTPases Activate NADPH Oxidases / regulation of protein phosphorylation / negative regulation of protein binding / positive regulation of GTPase activity / ciliary basal body / peptidyl-prolyl cis-trans isomerase activity / regulation of cytokinesis / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / phosphoprotein binding / Negative regulators of DDX58/IFIH1 signaling / peptidylprolyl isomerase / negative regulation of transforming growth factor beta receptor signaling pathway / synapse organization / regulation of protein stability / negative regulation of protein catabolic process / negative regulation of ERK1 and ERK2 cascade / tau protein binding / beta-catenin binding / neuron differentiation / ISG15 antiviral mechanism / positive regulation of canonical Wnt signaling pathway / positive regulation of protein binding / regulation of gene expression / midbody / cellular response to hypoxia / Regulation of TP53 Activity through Phosphorylation / positive regulation of protein phosphorylation / response to hypoxia / protein stabilization / nuclear speck / glutamatergic synapse / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Ubiquitin Ligase Nedd4; Chain: W; - #10 / Ubiquitin Ligase Nedd4; Chain: W; / : / Peptidyl-prolyl cis-trans isomerase, PpiC-type, conserved site / PpiC-type peptidyl-prolyl cis-trans isomerase signature. / PPIC-type PPIASE domain / PpiC-type peptidyl-prolyl cis-trans isomerase family profile. / Peptidyl-prolyl cis-trans isomerase, PpiC-type / Chitinase A; domain 3 - #40 / WW domain ...Ubiquitin Ligase Nedd4; Chain: W; - #10 / Ubiquitin Ligase Nedd4; Chain: W; / : / Peptidyl-prolyl cis-trans isomerase, PpiC-type, conserved site / PpiC-type peptidyl-prolyl cis-trans isomerase signature. / PPIC-type PPIASE domain / PpiC-type peptidyl-prolyl cis-trans isomerase family profile. / Peptidyl-prolyl cis-trans isomerase, PpiC-type / Chitinase A; domain 3 - #40 / WW domain / WW/rsp5/WWP domain signature. / Chitinase A; domain 3 / WW domain superfamily / WW/rsp5/WWP domain profile. / Domain with 2 conserved Trp (W) residues / WW domain / Peptidyl-prolyl cis-trans isomerase domain superfamily / Single Sheet / Roll / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Chem-4C0 / Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsBaker, L.M. / Dokurno, P. / Robinson, D.A. / Surgenor, A.E. / Murray, J.B. / Potter, A.J. / Moore, J.D.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Structure-guided design of alpha-amino acid-derived Pin1 inhibitors
Authors: Potter, A.J. / Ray, S. / Gueritz, L. / Nunns, C.L. / Bryant, C.J. / Scrace, S.F. / Matassova, N. / Baker, L.M. / Dokurno, P. / Robinson, D.A. / Surgenor, A.E. / Davis, B. / Murray, J.B. / ...Authors: Potter, A.J. / Ray, S. / Gueritz, L. / Nunns, C.L. / Bryant, C.J. / Scrace, S.F. / Matassova, N. / Baker, L.M. / Dokurno, P. / Robinson, D.A. / Surgenor, A.E. / Davis, B. / Murray, J.B. / Richardson, C.M. / Moore, J.D.
History
DepositionOct 19, 2009Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Dec 22, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 10, 2021Group: Database references / Derived calculations / Category: database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Nov 1, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,3513
Polymers18,4671
Non-polymers8842
Water2,972165
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)68.211, 68.211, 79.550
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 / Rotamase Pin1 / PPIase Pin1


Mass: 18467.475 Da / Num. of mol.: 1 / Mutation: R14A, Q131A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIN1 / Plasmid: PET28A / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE3) / References: UniProt: Q13526, peptidylprolyl isomerase
#2: Chemical ChemComp-4C0 / 3-(1H-benzimidazol-2-yl)-N-(3-phenylpropanoyl)-D-alanine / (R)-3-(1H-Benzoimidazol-2-yl)-2-(3-phenyl-propionylamino)-propionic acid


Mass: 337.372 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H19N3O3
#3: Chemical ChemComp-12P / DODECAETHYLENE GLYCOL / POLYETHYLENE GLYCOL PEG400


Mass: 546.646 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H50O13 / Comment: precipitant*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 165 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.89 Å3/Da / Density % sol: 57.48 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 2.2M Ammonium sulphate, 0.1M HEPES buffer, 1% PEG 400, 5mM DTT, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jul 7, 2006 / Details: mirrors
RadiationMonochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.9→59.07 Å / Num. all: 16740 / Num. obs: 16740 / % possible obs: 96.7 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 2.1 % / Rmerge(I) obs: 0.057 / Net I/σ(I): 5.8
Reflection shellResolution: 1.9→1.97 Å / Redundancy: 1.9 % / Rmerge(I) obs: 0.323 / Mean I/σ(I) obs: 1.9 / Num. unique all: 939 / % possible all: 92

-
Processing

Software
NameVersionClassification
CrystalCleardata collection
AMoREphasing
REFMAC5.5.0072refinement
d*TREKdata reduction
d*TREKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1PIN

1pin


Resolution: 1.95→29.54 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.927 / SU B: 3.327 / SU ML: 0.096 / Cross valid method: THROUGHOUT / ESU R: 0.144 / ESU R Free: 0.151 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.24829 785 5 %RANDOM
Rwork0.18775 ---
all0.19064 14798 --
obs0.19064 14798 97.13 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 29.024 Å2
Baniso -1Baniso -2Baniso -3
1-0.93 Å20.47 Å20 Å2
2--0.93 Å20 Å2
3----1.4 Å2
Refinement stepCycle: LAST / Resolution: 1.95→29.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1153 0 49 165 1367
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0250.0211229
X-RAY DIFFRACTIONr_angle_refined_deg2.0281.9821644
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.4475145
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.04222.10557
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.39115207
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.3091514
X-RAY DIFFRACTIONr_chiral_restr0.1450.2164
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.021934
X-RAY DIFFRACTIONr_mcbond_it1.3161.5724
X-RAY DIFFRACTIONr_mcangle_it2.21421159
X-RAY DIFFRACTIONr_scbond_it3.6943505
X-RAY DIFFRACTIONr_scangle_it5.6644.5484
LS refinement shellResolution: 1.95→2.001 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.37 63 -
Rwork0.307 1053 -
obs-1116 96.62 %

+
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