[English] 日本語
Yorodumi
- PDB-7tgu: Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7tgu
TitleStructure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B1
ComponentsPeptidyl-prolyl cis-trans isomerase F, mitochondrial
KeywordsISOMERASE/ISOMERASE inhibitor / Peptidyl-prolyl isomerase / oxidative stress / necrosis / mitochondrial permeability / ISOMERASE / ISOMERASE-ISOMERASE inhibitor complex
Function / homology
Function and homology information


: / : / mitochondrial outer membrane permeabilization involved in programmed cell death / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / skeletal muscle fiber differentiation / mitochondrial permeability transition pore complex / cellular response to arsenic-containing substance / negative regulation of ATP-dependent activity / mitochondrial depolarization / negative regulation of oxidative phosphorylation ...: / : / mitochondrial outer membrane permeabilization involved in programmed cell death / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / skeletal muscle fiber differentiation / mitochondrial permeability transition pore complex / cellular response to arsenic-containing substance / negative regulation of ATP-dependent activity / mitochondrial depolarization / negative regulation of oxidative phosphorylation / regulation of mitochondrial membrane permeability / cyclosporin A binding / negative regulation of release of cytochrome c from mitochondria / negative regulation of intrinsic apoptotic signaling pathway / necroptotic process / apoptotic mitochondrial changes / cellular response to calcium ion / response to ischemia / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / cellular response to hydrogen peroxide / protein folding / mitochondrial matrix / negative regulation of apoptotic process / mitochondrion / membrane / cytoplasm
Similarity search - Function
Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site / Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain profile. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain / Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD / Cyclophilin-like domain superfamily
Similarity search - Domain/homology
Chem-I44 / Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.21 Å
AuthorsRangwala, A.M. / Thakur, M.K. / Seeliger, M.A. / Peterson, A.A. / Liu, D.R.
Funding support United States, 6items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)CA260772 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM118062 United States
National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB)EB022376 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM119437 United States
National Institutes of Health/Office of the DirectorOD028478 United States
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Nat.Chem.Biol. / Year: 2022
Title: Discovery and molecular basis of subtype-selective cyclophilin inhibitors.
Authors: Peterson, A.A. / Rangwala, A.M. / Thakur, M.K. / Ward, P.S. / Hung, C. / Outhwaite, I.R. / Chan, A.I. / Usanov, D.L. / Mootha, V.K. / Seeliger, M.A. / Liu, D.R.
History
DepositionJan 9, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 24, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 12, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 2, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 18, 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
X: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,5502
Polymers17,6661
Non-polymers8841
Water2,288127
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)40.195, 60.141, 66.264
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Peptidyl-prolyl cis-trans isomerase F, mitochondrial / PPIase F / Cyclophilin D / CyP-D / CypD / Cyclophilin F / Mitochondrial cyclophilin / CyP-M / Rotamase F


Mass: 17666.150 Da / Num. of mol.: 1 / Mutation: K175I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPIF, CYP3 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P30405, peptidylprolyl isomerase
#2: Chemical ChemComp-I44 / (4S,7S,11R,13E,19S)-N-[2-(2-aminoethoxy)ethyl]-4-[(4-benzoylphenyl)methyl]-7-benzyl-3,6,12,15,21-pentaoxo-1,3,4,5,6,7,8,9,10,12,15,16,17,18,19,20,21,22-octadecahydro-2H-7,11-methano-2,5,11,16,20-benzopentaazacyclotetracosine-19-carboxamide


Mass: 884.030 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C50H57N7O8
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 127 / 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: 2.17 Å3/Da / Density % sol: 43.4 % / Description: Blades and tabular, between 0.3-0.5 mm
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.3
Details: 23% PEG 3350 0.5 M KH2PO4 Protein and inhibitor were mixed in ratio 1:3 1 uL of protein:inhibitor complex was mixed with 1 uL mother liquor

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-2 / Wavelength: 0.97933 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 30, 2019
RadiationMonochromator: Double Crystal Monochromator; Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97933 Å / Relative weight: 1
ReflectionResolution: 1.21→44.534 Å / Num. obs: 43493 / % possible obs: 87.8 % / Redundancy: 10.8 % / Biso Wilson estimate: 11.42 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.051 / Rpim(I) all: 0.015 / Rrim(I) all: 0.053 / Net I/σ(I): 23
Reflection shellResolution: 1.21→1.232 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.428 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 799 / CC1/2: 0.766 / CC star: 0.951 / Rpim(I) all: 0.317 / Rrim(I) all: 0.538 / % possible all: 33.4

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
Cootmodel building
XDSdata reduction
autoPROCdata processing
PHASERphasing
XDSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2BIT

2bit


Resolution: 1.21→44.53 Å / SU ML: 0.0933 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 16.1107
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1604 2108 4.85 %
Rwork0.1513 41381 -
obs0.1518 43489 87.74 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 15.3 Å2
Refinement stepCycle: LAST / Resolution: 1.21→44.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1229 0 65 127 1421
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00771370
X-RAY DIFFRACTIONf_angle_d1.07641852
X-RAY DIFFRACTIONf_chiral_restr0.0819195
X-RAY DIFFRACTIONf_plane_restr0.0071242
X-RAY DIFFRACTIONf_dihedral_angle_d20.3353197
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.21-1.240.2397600.21471082X-RAY DIFFRACTION35.42
1.24-1.270.1941780.19731576X-RAY DIFFRACTION50.71
1.27-1.30.19711040.18362026X-RAY DIFFRACTION65.52
1.3-1.340.20281260.17942417X-RAY DIFFRACTION77.98
1.34-1.390.19591250.16632770X-RAY DIFFRACTION88.24
1.39-1.440.17581330.15833000X-RAY DIFFRACTION95.69
1.44-1.490.1831620.14183102X-RAY DIFFRACTION100
1.49-1.560.13731650.13373115X-RAY DIFFRACTION100
1.56-1.640.14221640.12993125X-RAY DIFFRACTION99.97
1.64-1.750.15511930.13773110X-RAY DIFFRACTION99.97
1.75-1.880.14571530.14553141X-RAY DIFFRACTION100
1.88-2.070.16191570.14493172X-RAY DIFFRACTION100
2.07-2.370.15531690.14133169X-RAY DIFFRACTION100
2.37-2.990.15141630.15763218X-RAY DIFFRACTION100
2.99-44.530.16371560.1573358X-RAY DIFFRACTION99.63
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)
11.44038036349-0.4135710169410.2590156314141.46614030251-0.4737323467941.12899706652-0.055585812927-0.179840590985-0.155944190310.0922293515580.031373765730.03412789434740.1273654478090.02367101466880.01192798462630.08869483811290.0178432027340.02125064635910.09440900848040.02210373026110.07075260946237.4332749295762.760467862673.5508193817
23.53828004679-0.861239714843-0.5255921905961.64378366460.3077226486191.04864821261-0.0474282382476-0.00895983106965-0.3363192173650.006452108912170.01041595638180.1221387821710.1278754994420.01673971623940.05793866951130.110614129322-0.00651628190231-0.005095395257520.08573415448450.0006910759239880.1325077760598.1160857773555.987594243965.0742322363
31.42570798735-0.943893923552-0.5097853460694.168212471071.839497035750.819860834725-0.02614755872420.296965946531-0.301165690363-0.00412185195748-0.2348748994420.4288789503340.0916857933494-0.19113647550.2323183494180.10342266035-0.0143057115096-0.0007003815869560.146830923702-0.05041020140550.1707974896010.66779954125159.143216004459.1132210113
41.197109979020.00215840543759-0.03437742089851.47259570011-0.1591240919360.9642710487730.02427464707920.110286795997-0.00936393393011-0.0687111360971-0.0456749653099-0.09302326377050.05572933221420.05295008149380.02056221427060.08347664253070.007536803652810.007540052487590.0951079506560.00208140366520.075651605581714.735085988366.016493967661.3983157737
51.94951774568-0.2340237907640.5411356905012.63633344433-0.6729464952921.13455783276-0.068770532984-0.0742948797238-0.007287196292270.08866615967280.0192292195144-0.111726303206-0.03482467957650.1338354771240.08190898591480.05325512311790.0143874791436-0.000404814309640.08851637800840.00470593166060.071965025872515.502505768166.455028332767.0022904844
63.62457470260.208481770371-1.151284927617.253738306432.830576754763.28143288392-0.180414293042-0.229682446068-0.2898426358750.3125392084540.214776726344-0.2001754160360.2443685285520.154852642972-0.0185851266180.1862254008860.05250026991150.003522362675890.1487164143770.04374482766860.16773690829418.848627277351.568004127372.0686202295
72.66467072892-1.46155919803-1.571643312052.544199262861.105182445252.44810982259-0.250546138367-0.0634524529304-0.5874775327320.2396076882260.07804869794360.2209568586550.4054749511840.06512956418450.148653457490.1383185240880.008607176279270.01164964052920.1064500244850.01730907696890.2264276487239.8265548059150.854384630169.019202978
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'X' and (resid 3 through 42 )
2X-RAY DIFFRACTION2chain 'X' and (resid 43 through 65 )
3X-RAY DIFFRACTION3chain 'X' and (resid 66 through 85 )
4X-RAY DIFFRACTION4chain 'X' and (resid 86 through 123 )
5X-RAY DIFFRACTION5chain 'X' and (resid 124 through 136 )
6X-RAY DIFFRACTION6chain 'X' and (resid 137 through 146 )
7X-RAY DIFFRACTION7chain 'X' and (resid 147 through 165 )

+
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