[English] 日本語
Yorodumi
- PDB-5m6e: Small Molecule inhibitors of IAP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5m6e
TitleSmall Molecule inhibitors of IAP
ComponentsE3 ubiquitin-protein ligase XIAP
KeywordsAPOPTOSIS / XIAP / metal-binding / inhibitor / Xiap#1
Function / homology
Function and homology information


endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway ...endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway / SMAC, XIAP-regulated apoptotic response / Regulation of the apoptosome activity / Activation of caspases through apoptosome-mediated cleavage / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / TNFR1-induced proapoptotic signaling / regulation of innate immune response / RIPK1-mediated regulated necrosis / cysteine-type endopeptidase inhibitor activity / protein K63-linked ubiquitination / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of type I interferon production / negative regulation of tumor necrosis factor-mediated signaling pathway / Regulation of PTEN localization / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of protein ubiquitination / Deactivation of the beta-catenin transactivating complex / Regulation of TNFR1 signaling / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / Regulation of necroptotic cell death / Wnt signaling pathway / Regulation of PTEN stability and activity / ubiquitin-protein transferase activity / positive regulation of canonical Wnt signaling pathway / ubiquitin protein ligase activity / regulation of cell population proliferation / regulation of inflammatory response / neuron apoptotic process / regulation of apoptotic process / positive regulation of canonical NF-kappaB signal transduction / regulation of cell cycle / defense response to bacterium / DNA damage response / negative regulation of apoptotic process / nucleoplasm / identical protein binding / metal ion binding / nucleus / cytosol / cytoplasm
Similarity search - Function
XIAP/BIRC8, UBA domain / : / BIRC2/3-like, UBA domain / Inhibitor Of Apoptosis Protein (2mihbC-IAP-1); Chain A / Inhibitor Of Apoptosis Protein (2mihbC-IAP-1); Chain A / BIR repeat. / BIR repeat / Inhibitor of Apoptosis domain / BIR repeat profile. / Baculoviral inhibition of apoptosis protein repeat ...XIAP/BIRC8, UBA domain / : / BIRC2/3-like, UBA domain / Inhibitor Of Apoptosis Protein (2mihbC-IAP-1); Chain A / Inhibitor Of Apoptosis Protein (2mihbC-IAP-1); Chain A / BIR repeat. / BIR repeat / Inhibitor of Apoptosis domain / BIR repeat profile. / Baculoviral inhibition of apoptosis protein repeat / Zinc finger, C3HC4 type (RING finger) / Death-like domain superfamily / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-7HT / E3 ubiquitin-protein ligase XIAP
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2.32 Å
AuthorsWilliams, P.A.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP).
Authors: Tamanini, E. / Buck, I.M. / Chessari, G. / Chiarparin, E. / Day, J.E.H. / Frederickson, M. / Griffiths-Jones, C.M. / Hearn, K. / Heightman, T.D. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / ...Authors: Tamanini, E. / Buck, I.M. / Chessari, G. / Chiarparin, E. / Day, J.E.H. / Frederickson, M. / Griffiths-Jones, C.M. / Hearn, K. / Heightman, T.D. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Peakman, T. / Reader, M. / Rich, S.J. / Ward, G.A. / Williams, P.A. / Wilsher, N.E.
History
DepositionOct 25, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 24, 2017Provider: repository / Type: Initial release
Revision 2.0Jun 28, 2017Group: Database references / Non-polymer description / Structure summary
Category: citation / entity
Item: _chem_comp.formula / _chem_comp.name ..._chem_comp.formula / _chem_comp.name / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _entity.formula_weight / _entity.pdbx_description

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase XIAP
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,2155
Polymers14,5751
Non-polymers6404
Water3,729207
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area410 Å2
ΔGint-4 kcal/mol
Surface area6450 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.525, 71.525, 105.693
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number91
Space group name H-MP4122
Components on special symmetry positions
IDModelComponents
11A-402-

NA

21A-532-

HOH

31A-637-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein E3 ubiquitin-protein ligase XIAP / Baculoviral IAP repeat-containing protein 4 / IAP-like protein / hILP / Inhibitor of apoptosis ...Baculoviral IAP repeat-containing protein 4 / IAP-like protein / hILP / Inhibitor of apoptosis protein 3 / hIAP3 / X-linked inhibitor of apoptosis protein / X-linked IAP


Mass: 14575.300 Da / Num. of mol.: 1
Mutation: deletion 1-248, deletion 355-497, insertion 240 MGSSHHHHHHSSGLVPRGSH
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P98170, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases)

-
Non-polymers , 5 types, 211 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#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-7HT / 1-[3,3-dimethyl-6-(phenylmethyl)-2~{H}-pyrrolo[3,2-c]pyridin-1-yl]-2-[(2~{R},5~{R})-5-methyl-2-[(4-methylpyrazol-1-yl)methyl]piperazin-4-ium-1-yl]ethanone


Mass: 473.633 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H37N6O
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 207 / 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: 4.64 Å3/Da / Density % sol: 73.48 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 3.2M NaCl, 0.1M HEPES/NaOHpH=8

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54187 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: May 19, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54187 Å / Relative weight: 1
ReflectionResolution: 2.284→28.909 Å / Num. obs: 12468 / % possible obs: 95.6 % / Redundancy: 2.4 % / Rmerge(I) obs: 0.039 / Net I/σ(I): 17.5
Reflection shellResolution: 2.31→2.41 Å / Rmerge(I) obs: 0.207 / Mean I/σ(I) obs: 4.4 / % possible all: 85.3

-
Processing

Software
NameVersionClassification
REFMAC5.8.0135refinement
XDSdata reduction
SCALAdata scaling
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.32→28.909 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.913 / SU B: 8.075 / SU ML: 0.119 / Cross valid method: THROUGHOUT / ESU R: 0.182 / ESU R Free: 0.183 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23923 646 5.4 %RANDOM
Rwork0.18326 ---
obs0.18621 11208 95.04 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 43.572 Å2
Baniso -1Baniso -2Baniso -3
1--0.09 Å20 Å2-0 Å2
2---0.09 Å2-0 Å2
3---0.18 Å2
Refinement stepCycle: 1 / Resolution: 2.32→28.909 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms860 0 41 207 1108
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.019961
X-RAY DIFFRACTIONr_bond_other_d0.0020.02853
X-RAY DIFFRACTIONr_angle_refined_deg1.4791.9131314
X-RAY DIFFRACTIONr_angle_other_deg1.0072.8991978
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5965114
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.41424.73152
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.15115.19158
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.559153
X-RAY DIFFRACTIONr_chiral_restr0.1040.2124
X-RAY DIFFRACTIONr_gen_planes_refined0.0020.0211105
X-RAY DIFFRACTIONr_gen_planes_other00.02238
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_it2.8485.708433
X-RAY DIFFRACTIONr_mcbond_other2.8465.688432
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.7136.589528
X-RAY DIFFRACTIONr_scbond_other3.7096.59529
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined8.2913.613332
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.319→2.379 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.25 36 -
Rwork0.24 706 -
obs--83.46 %
Refinement TLS params.Method: refined / Origin x: -17.1938 Å / Origin y: -28.9723 Å / Origin z: -4.2808 Å
111213212223313233
T0.0379 Å2-0.0216 Å20.0065 Å2-0.1037 Å2-0.0276 Å2--0.0087 Å2
L6.1948 °2-0.5452 °21.3642 °2-2.9851 °2-0.059 °2--3.1955 °2
S0.0856 Å °-0.2554 Å °0.0102 Å °0.2968 Å °-0.0385 Å °0.0206 Å °-0.0587 Å °-0.0274 Å °-0.0471 Å °

+
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