[English] 日本語
Yorodumi
- PDB-8gh7: 142D6 bound to BIR3-XIAP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8gh7
Title142D6 bound to BIR3-XIAP
Components
  • BIR3 inhibitor MAA-CHG-PRO-ZHW
  • E3 ubiquitin-protein ligase XIAP
KeywordsSIGNALING PROTEIN/INHIBITOR / BIR Domain / protein-ligand complex / BIR3 inhibitor / zinc finger motif / SIGNALING PROTEIN / SIGNALING PROTEIN-INHIBITOR complex
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 / 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 ...XIAP/BIRC8, UBA domain / : / BIRC2/3-like, UBA domain / 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
Similarity search - Domain/homology
: / Chem-7PE / E3 ubiquitin-protein ligase XIAP
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsGarza-Granados, A. / McGuire, J. / Baggio, C. / Pellecchia, M. / Pegan, S.D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA168517A1 United States
CitationJournal: J.Med.Chem. / Year: 2023
Title: Characterization of a Potent and Orally Bioavailable Lys-Covalent Inhibitor of Apoptosis Protein (IAP) Antagonist.
Authors: Udompholkul, P. / Garza-Granados, A. / Alboreggia, G. / Baggio, C. / McGuire, J. / Pegan, S.D. / Pellecchia, M.
History
DepositionMar 9, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 5, 2023Provider: repository / Type: Initial release
Revision 2.0Jul 12, 2023Group: Derived calculations / Non-polymer description / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_molecule_features / struct_conn
Item: _chem_comp.formula / _chem_comp.formula_weight ..._chem_comp.formula / _chem_comp.formula_weight / _chem_comp.name / _entity.formula_weight / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase XIAP
B: E3 ubiquitin-protein ligase XIAP
D: BIR3 inhibitor MAA-CHG-PRO-ZHW
H: BIR3 inhibitor MAA-CHG-PRO-ZHW
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,5968
Polymers23,8454
Non-polymers7524
Water1,62190
1
A: E3 ubiquitin-protein ligase XIAP
D: BIR3 inhibitor MAA-CHG-PRO-ZHW
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,2984
Polymers11,9222
Non-polymers3762
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: E3 ubiquitin-protein ligase XIAP
H: BIR3 inhibitor MAA-CHG-PRO-ZHW
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,2984
Polymers11,9222
Non-polymers3762
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)34.171, 55.150, 93.033
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 11369.703 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Production host: Escherichia coli (E. coli)
References: UniProt: P98170, RING-type E3 ubiquitin transferase
#2: Protein/peptide BIR3 inhibitor MAA-CHG-PRO-ZHW


Type: Peptide-like / Class: Inhibitor / Mass: 552.658 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: Lys-covalent pan-IAP inhibitor / Source: (synth.) synthetic construct (others) / References: BIRD: PRD_002528
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-7PE / 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL / POLYETHYLENE GLYCOL FRAGMENT / Polyethylene glycol


Mass: 310.384 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H30O7 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 90 / 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: 1.82 Å3/Da / Density % sol: 32.39 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 0.1 M HEPES pH 7.5, 35% isopropanol and 18% PEG 4000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97934 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 16, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97934 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. obs: 18803 / % possible obs: 98.9 % / Redundancy: 3.6 % / CC1/2: 0.972 / Rpim(I) all: 0.059 / Rrim(I) all: 0.158 / Χ2: 1.05 / Net I/σ(I): 13.4
Reflection shellResolution: 1.75→1.78 Å / Redundancy: 5.7 % / Num. unique obs: 1695 / CC1/2: 0.846 / CC star: 0.957 / Rrim(I) all: 0.763 / Χ2: 0.508 / % possible all: 98.9

-
Processing

Software
NameVersionClassification
PHENIX1.19.2refinement
HKL-2000data scaling
HKL-2000data reduction
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.75→35.56 Å / SU ML: 0.16 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 23.48 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2091 899 4.92 %
Rwork0.1775 --
obs0.1791 18275 99.23 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.75→35.56 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1582 0 34 90 1706
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0031671
X-RAY DIFFRACTIONf_angle_d0.6442257
X-RAY DIFFRACTIONf_dihedral_angle_d10.616249
X-RAY DIFFRACTIONf_chiral_restr0.044214
X-RAY DIFFRACTIONf_plane_restr0.005282
LS refinement shellResolution: 1.75→1.86 Å
RfactorNum. reflection% reflection
Rfree0.2772 146 -
Rwork0.2259 2830 -
obs--99 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.5836-0.2490.77462.0611-0.17542.986-0.14780.0024-0.1373-0.0457-0.0015-0.23890.13180.0958-0.02350.2073-0.0098-0.01640.1827-0.00370.225737.427615.737659.0338
21.4151-0.1603-0.16481.64150.32321.5582-0.04890.1008-0.0397-0.31760.04420.1332-0.0743-0.17080.00420.2255-0.0344-0.03450.219-0.00070.204829.90221.465956.251
32.3986-0.5073-0.46093.8218-0.65582.04740.1594-0.01080.10530.03660.00730.1665-0.2128-0.0374-0.0010.2429-0.0379-0.00720.19290.0130.219336.411233.601356.8265
44.21430.5856-1.09084.249-1.04084.2577-0.2246-0.7783-0.87720.1785-0.22420.3530.56650.20780.02370.3821-0.00990.06170.35450.08410.330514.539842.526372.3446
50.4102-0.06740.4380.2120.5952.9269-0.00620.0360.30740.01040.04760.3847-0.3262-0.5767-0.05110.27550.02940.00280.2805-0.01840.351610.893154.193863.4032
64.6435-0.2807-0.60132.2898-0.41752.83450.1644-0.07670.4635-0.16230.0729-0.0566-0.57190.2813-0.01550.4447-0.01850.00730.3560.12780.444219.180657.167251.9087
75.2537-0.24910.83327.03431.0965.92530.07850.6539-0.0865-0.4058-0.20471.2836-0.2918-1.1952-0.16060.25810.0438-0.07120.38740.00370.335911.827750.70154.5695
81.96171.1336-1.4392.6955-0.58871.7087-0.1741-0.0360.1813-0.10360.0624-0.0855-0.18570.1480.00890.1915-0.0358-0.02350.21160.01430.246521.166752.169161.0962
91.08150.0169-0.02040.9515-0.57962.4152-0.05710.1337-0.0026-0.26890.10330.07810.00730.15270.0220.2139-0.0471-0.02880.24150.02620.234521.542646.743656.25
102.4678-0.29060.82341.9308-0.74791.1404-0.0440.1796-0.1662-0.3142-0.1276-0.00940.09220.02020.00380.3089-0.0427-0.01750.202-0.00840.222219.980440.008857.1518
112.3783-0.26840.52853.88960.52791.93680.03910.1001-0.04330.0367-0.0499-0.1970.29660.1136-0.01070.2299-0.0573-0.05310.2232-0.00340.224914.231134.094656.7121
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 253 through 291 )
2X-RAY DIFFRACTION2chain 'A' and (resid 292 through 327 )
3X-RAY DIFFRACTION3chain 'A' and (resid 328 through 345 )
4X-RAY DIFFRACTION4chain 'B' and (resid 254 through 259 )
5X-RAY DIFFRACTION5chain 'B' and (resid 260 through 272 )
6X-RAY DIFFRACTION6chain 'B' and (resid 273 through 280 )
7X-RAY DIFFRACTION7chain 'B' and (resid 281 through 286 )
8X-RAY DIFFRACTION8chain 'B' and (resid 287 through 300 )
9X-RAY DIFFRACTION9chain 'B' and (resid 301 through 315 )
10X-RAY DIFFRACTION10chain 'B' and (resid 316 through 327 )
11X-RAY DIFFRACTION11chain 'B' and (resid 328 through 345 )

+
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