[English] 日本語
Yorodumi
- PDB-7th6: Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7th6
TitleStructure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B21
ComponentsPeptidyl-prolyl cis-trans isomerase F, mitochondrial
KeywordsISOMERASE / oxidative stress / necrosis / mitochondrial permeability
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 / apoptotic mitochondrial changes / necroptotic process / 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-I56 / Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 0.97 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 10, 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
A: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,5662
Polymers17,6521
Non-polymers9141
Water3,513195
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)38.632, 38.632, 103.509
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number78
Space group name H-MP43
Space group name HallP4cw
Symmetry operation#1: x,y,z
#2: -y,x,z+3/4
#3: y,-x,z+1/4
#4: -x,-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: 17652.125 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) / Strain (production host): BL21(DE3) / References: UniProt: P30405, peptidylprolyl isomerase
#2: Chemical ChemComp-I56 / 4'-{[(4S,7S,11R,13E,19S)-19-{[2-(2-aminoethoxy)ethyl]carbamoyl}-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-benzopentaazacyclotetracosin-4-yl]methyl}-2-methyl[1,1'-biphenyl]-4-carboxylic acid


Mass: 914.056 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C51H59N7O9 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 195 / 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: 2.08 Å3/Da / Density % sol: 40.9 % / Description: Bladed, tabular, roughly 0.3-0.5 mm in length
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.3
Details: 20% PEG 3350 0.5 M KH2PO4 Protein and inhibitor were mixed in ratio 1:2 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: 0.92016 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 4, 2019
RadiationMonochromator: Double Crystal Monochromator; Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92016 Å / Relative weight: 1
ReflectionResolution: 0.97→30.96 Å / Num. obs: 82203 / % possible obs: 92.15 % / Redundancy: 12.5 % / Biso Wilson estimate: 7.71 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.107 / Rpim(I) all: 0.029 / Rrim(I) all: 0.112 / Net I/σ(I): 13.1
Reflection shellResolution: 0.97→1 Å / Redundancy: 3.6 % / Rmerge(I) obs: 1.364 / Mean I/σ(I) obs: 0.9 / Num. unique obs: 2612 / CC1/2: 0.241 / CC star: 0.635 / Rpim(I) all: 0.828 / Rrim(I) all: 1.615 / % possible all: 61.6

-
Processing

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

2bit


Resolution: 0.97→30.96 Å / SU ML: 0.1009 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 15.6135
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1519 1997 2.43 %
Rwork0.1365 80206 -
obs0.1369 82203 92.15 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 10.72 Å2
Refinement stepCycle: LAST / Resolution: 0.97→30.96 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1236 0 67 195 1498
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01211382
X-RAY DIFFRACTIONf_angle_d1.27951872
X-RAY DIFFRACTIONf_chiral_restr0.1094194
X-RAY DIFFRACTIONf_plane_restr0.0143246
X-RAY DIFFRACTIONf_dihedral_angle_d12.1744264
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
0.97-0.990.3526720.34123179X-RAY DIFFRACTION51.06
0.99-1.020.3011050.29074257X-RAY DIFFRACTION69.08
1.02-1.050.2681230.22594873X-RAY DIFFRACTION78.6
1.05-1.090.18451450.1845844X-RAY DIFFRACTION94.42
1.09-1.120.14371590.15286235X-RAY DIFFRACTION99.95
1.12-1.170.151530.14316212X-RAY DIFFRACTION99.89
1.17-1.220.15391530.13536179X-RAY DIFFRACTION99.84
1.22-1.290.14631550.12986215X-RAY DIFFRACTION99.86
1.29-1.370.1341540.12536217X-RAY DIFFRACTION99.83
1.37-1.470.15191540.12216178X-RAY DIFFRACTION99.62
1.47-1.620.13891570.12126148X-RAY DIFFRACTION98.84
1.62-1.860.12591530.12266151X-RAY DIFFRACTION98.87
1.86-2.340.12741560.1166238X-RAY DIFFRACTION99.95
2.34-30.960.15931580.13386280X-RAY DIFFRACTION99.98
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)
10.204477730075-0.2211767731030.03643902576220.4711357273850.1557249648740.663633863689-0.03605920773560.0469848590041-0.0159442926113-0.0442011058908-0.007818098339710.02815423482590.00406185645669-0.04128718325190.0001639131371840.06728402060960.00211379710683-0.003542017282250.0728280710186-0.01453365787440.07490462779162.44563448542-16.07305885285.23555911801
20.345393420102-0.0990281840412-0.03992047702070.2156762027120.1178261009960.2219436943710.01113119072330.0283097855252-0.0376745492064-0.001681899822310.0224566260577-0.04940660985370.007868607123730.0582902784880.0002472271627420.0575892228907-0.000770496586247-0.001804819172490.070278047759-0.009865806566820.077873179107515.2127323269-12.682164740813.9756176246
30.6015785284690.459181720485-0.1333275254180.5333181748450.2063004268710.5490310559370.0181529000857-0.00161813323218-0.0597021546380.039412045474-0.02900023411720.03883225236280.0359225449988-0.02385809788980.002700765237020.0627625255278-0.00169219828268-0.003299868604440.06976212676960.002445084307580.06821603085320.0370834886169-12.632933615615.6567325453
40.111551226081-0.125041034403-0.0254689664730.145723689821-0.0009124526264080.159303086258-0.00381290787771-0.132693017317-0.1101475175590.0819411998526-0.0252404591916-0.008307974832310.0662746642420.0246714549930.001286411260120.079844393810.00128831917835-0.0007717836526220.09471148063130.0167582736950.0857516704766.0944770037-14.984741714324.7525693346
50.4388484962070.0854274451284-0.06293088806430.3043295121060.1492810854160.3715940029080.0146615179661-0.007316561426740.0415976805274-0.0109565715202-0.00444307865141-0.00583709056655-0.0971653881963-0.005307449446160.0001389656557560.06195404911920.002728216451460.00197441873540.0593965155489-0.0008031469969640.0550847586547.0250752922-2.0829110785516.5081928576
60.4116735434990.1181728760010.03771290139060.569572292232-0.1902174291260.3472352116070.00749257531010.0291911835193-0.00694015160454-0.04763480898350.0256692960811-0.00392362112018-0.07447373916460.04262062626110.008170592237620.05972011741980.00243778723031-0.002259653443940.0552761197847-0.002711192612680.05896649093958.81013383379-3.8968771038510.8562541691
70.1118665957580.004342499658610.1022993293550.04529217316560.04016897981320.2921022009430.07120074322250.1448650809830.0955586832513-0.0567673842594-0.0003501532641020.103628807841-0.0875547730337-0.13749395352-0.001449370115930.08841828004840.00114460029169-0.01246043800720.109560411550.003789742255370.102389748038-5.29405860088-8.311785985494.30413140418
80.268657152254-0.1165503016880.1645623911210.0656154725102-0.1099139737060.199441882310.0217811005914-0.01486110869970.01032100274090.0839177462854-0.07627320888440.209669255629-0.00830791102475-0.0712398238558-0.01628293265480.07462252262720.00173113041510.005119179178810.110823151345-0.01320522427880.15174447611-12.3643818402-9.2800906286414.610080943
90.0506993663539-0.01575188385880.06885140963690.118042998910.07142960725330.169611431211-0.02012221191190.01267536222840.000473779152297-0.03459228082220.0194452964539-0.02775904474090.03722054506560.0240331482073-0.005798696411050.07986569434390.00191106162620.001739173697740.082222265263-0.01338990013710.09409988293634.75469149787-19.68751763597.8666265211
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 45 through 66 )
2X-RAY DIFFRACTION2chain 'A' and (resid 67 through 83 )
3X-RAY DIFFRACTION3chain 'A' and (resid 84 through 106 )
4X-RAY DIFFRACTION4chain 'A' and (resid 107 through 126 )
5X-RAY DIFFRACTION5chain 'A' and (resid 127 through 164 )
6X-RAY DIFFRACTION6chain 'A' and (resid 165 through 177 )
7X-RAY DIFFRACTION7chain 'A' and (resid 178 through 187 )
8X-RAY DIFFRACTION8chain 'A' and (resid 188 through 197 )
9X-RAY DIFFRACTION9chain 'A' and (resid 198 through 207 )

+
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