[English] 日本語
Yorodumi
- PDB-4tot: Crystal structure of rat cyclophilin D in complex with a potent n... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4tot
TitleCrystal structure of rat cyclophilin D in complex with a potent nonimmunosuppressive inhibitor
Components
  • Peptidyl-prolyl cis-trans isomerase F, mitochondrial
  • nonimmunosuppressive inhibitor
KeywordsISOMERASE/ISOMERASE Inhibitor / Inhibitor / Complex / Cyclosporin / ISOMERASE-ISOMERASE Inhibitor complex
Function / homology
Function and homology information


: / regulation of proton-transporting ATPase activity, rotational mechanism / negative regulation of oxidative phosphorylation uncoupler activity / mitochondrial outer membrane permeabilization involved in programmed cell death / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / mitochondrial permeability transition pore complex / cellular response to arsenic-containing substance / negative regulation of ATP-dependent activity / negative regulation of oxidative phosphorylation / regulation of mitochondrial membrane permeability ...: / regulation of proton-transporting ATPase activity, rotational mechanism / negative regulation of oxidative phosphorylation uncoupler activity / mitochondrial outer membrane permeabilization involved in programmed cell death / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / mitochondrial permeability transition pore complex / cellular response to arsenic-containing substance / negative regulation of ATP-dependent activity / negative regulation of oxidative phosphorylation / regulation of mitochondrial membrane permeability / cyclosporin A binding / negative regulation of release of cytochrome c from mitochondria / apoptotic mitochondrial changes / necroptotic process / positive regulation of release of cytochrome c from mitochondria / negative regulation of intrinsic apoptotic signaling pathway / protein peptidyl-prolyl isomerization / cellular response to calcium ion / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / response to ischemia / peptide binding / cellular response to hydrogen peroxide / protein folding / regulation of apoptotic process / response to oxidative stress / mitochondrial inner membrane / mitochondrial matrix / intracellular membrane-bounded organelle / negative regulation of apoptotic process / mitochondrion / cytoplasm
Similarity search - Function
Cyclophilin-like / Cyclophilin / 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 / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
nonimmunosuppressive inhibitor / Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
synthetic construct (others)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.39 Å
AuthorsKnapp, M.S. / Elling, R.A.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Potent nonimmunosuppressive cyclophilin inhibitors with improved pharmaceutical properties and decreased transporter inhibition.
Authors: Fu, J. / Tjandra, M. / Becker, C. / Bednarczyk, D. / Capparelli, M. / Elling, R. / Hanna, I. / Fujimoto, R. / Furegati, M. / Karur, S. / Kasprzyk, T. / Knapp, M. / Leung, K. / Li, X. / Lu, P. ...Authors: Fu, J. / Tjandra, M. / Becker, C. / Bednarczyk, D. / Capparelli, M. / Elling, R. / Hanna, I. / Fujimoto, R. / Furegati, M. / Karur, S. / Kasprzyk, T. / Knapp, M. / Leung, K. / Li, X. / Lu, P. / Mergo, W. / Miault, C. / Ng, S. / Parker, D. / Peng, Y. / Roggo, S. / Rivkin, A. / Simmons, R.L. / Wang, M. / Wiedmann, B. / Weiss, A.H. / Xiao, L. / Xie, L. / Xu, W. / Yifru, A. / Yang, S. / Zhou, B. / Sweeney, Z.K.
History
DepositionJun 6, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 12, 2014Provider: repository / Type: Initial release
Revision 1.1Dec 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description / Source and taxonomy
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / entity_src_gen / pdbx_database_status / pdbx_entity_src_syn / pdbx_struct_oper_list / refine_hist / struct_conn / struct_ref_seq
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible / _pdbx_entity_src_syn.pdbx_alt_source_flag / _pdbx_struct_oper_list.symmetry_operation / _refine_hist.number_atoms_solvent / _refine_hist.number_atoms_total / _refine_hist.pdbx_number_atoms_nucleic_acid / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq.db_align_beg / _struct_ref_seq.db_align_end
Revision 1.2Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
B: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
C: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
D: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
E: nonimmunosuppressive inhibitor
F: nonimmunosuppressive inhibitor
G: nonimmunosuppressive inhibitor
H: nonimmunosuppressive inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,54114
Polymers76,2208
Non-polymers1,3216
Water5,368298
1
A: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
E: nonimmunosuppressive inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,4334
Polymers19,0552
Non-polymers3782
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1450 Å2
ΔGint-16 kcal/mol
Surface area7790 Å2
MethodPISA
2
B: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
F: nonimmunosuppressive inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,4334
Polymers19,0552
Non-polymers3782
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1480 Å2
ΔGint-18 kcal/mol
Surface area7860 Å2
MethodPISA
3
C: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
G: nonimmunosuppressive inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,3373
Polymers19,0552
Non-polymers2821
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1380 Å2
ΔGint-9 kcal/mol
Surface area7760 Å2
MethodPISA
4
D: Peptidyl-prolyl cis-trans isomerase F, mitochondrial
H: nonimmunosuppressive inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,3373
Polymers19,0552
Non-polymers2821
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1360 Å2
ΔGint-9 kcal/mol
Surface area7700 Å2
MethodPISA
Unit cell
Length a, b, c (Å)50.197, 57.286, 75.274
Angle α, β, γ (deg.)89.95, 83.81, 89.86
Int Tables number1
Space group name H-MP1

-
Components

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


Mass: 17692.166 Da / Num. of mol.: 4 / Fragment: UNP residues 43-206
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Ppif / Details (production host): pET30b / Production host: Escherichia coli (E. coli) / References: UniProt: P29117, peptidylprolyl isomerase
#2: Protein/peptide
nonimmunosuppressive inhibitor


Type: Cyclic peptide / Class: Inhibitor / Mass: 1362.825 Da / Num. of mol.: 4 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) / References: nonimmunosuppressive inhibitor
#3: Chemical
ChemComp-P6G / HEXAETHYLENE GLYCOL / POLYETHYLENE GLYCOL PEG400 / Polyethylene glycol


Mass: 282.331 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C12H26O7 / Comment: precipitant*YM
#4: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 298 / 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: 3.04 Å3/Da / Density % sol: 59.55 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 100 mM MES pH 6.5, 5% (v/v) PEG 400, 2M ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: Bruker Platinum 135 / Detector: CCD / Date: Sep 28, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.39→45.47 Å / Num. obs: 30008 / % possible obs: 90.94 % / Redundancy: 3.22 % / Biso Wilson estimate: 33.71 Å2 / Net I/σ(I): 7.82

-
Processing

SoftwareName: BUSTER / Version: 2.11.4 / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: in-house structure

Resolution: 2.39→30.3 Å / Cor.coef. Fo:Fc: 0.9005 / Cor.coef. Fo:Fc free: 0.8677 / SU R Cruickshank DPI: 0.54 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.416 / SU Rfree Blow DPI: 0.241 / SU Rfree Cruickshank DPI: 0.247
RfactorNum. reflection% reflectionSelection details
Rfree0.2298 1517 5.06 %RANDOM
Rwork0.1961 ---
obs0.1978 29998 90.94 %-
Displacement parametersBiso mean: 19.55 Å2
Baniso -1Baniso -2Baniso -3
1--0.1115 Å2-0.4018 Å21.2694 Å2
2---2.0381 Å2-0.9374 Å2
3---2.1496 Å2
Refine analyzeLuzzati coordinate error obs: 0.3 Å
Refinement stepCycle: 1 / Resolution: 2.39→30.3 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4976 0 1376 298 6650
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0096168HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.18900HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2096SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes116HARMONIC2
X-RAY DIFFRACTIONt_gen_planes808HARMONIC5
X-RAY DIFFRACTIONt_it6168HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.83
X-RAY DIFFRACTIONt_other_torsion14.98
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion708SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies8HARMONIC1
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact7267SEMIHARMONIC4
LS refinement shellResolution: 2.39→2.47 Å / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.3013 98 4.73 %
Rwork0.219 1973 -
all0.2229 2071 -
obs--90.94 %
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)
10.42440.26570.00241.18930.05510.8602-0.00140.0251-0.0311-0.04470.043-0.09430.00180.0885-0.04150.04920.0066-0.0329-0.1202-0.0184-0.0756-13.032-16.09692.5827
20.2042-0.1741-0.02161.4303-0.02551.0433-0.0234-0.0294-0.04210.03540.02980.1141-0.0105-0.0522-0.00640.05390.0071-0.0382-0.10630.0046-0.0892-18.269212.583619.8755
30.75680.12750.61691.46610.45150.6272-0.00420.18990.0286-0.06070.0545-0.0207-0.03630.1566-0.05020.0349-0.0002-0.0416-0.08070.0047-0.1075-27.7173-17.355747.0278
40.8004-0.00440.51410.5828-0.33170.9933-0.0043-0.1978-0.0210.0710.087-0.0308-0.0544-0.1852-0.08270.04890.0227-0.0434-0.0819-0.0061-0.09494.610611.316450.2134
50.03840.15280.10280.1222-0.1634-0.02260.00420.0127-0.00850.0711-0.00850.05290.0073-0.04860.00430.09080.0277-0.0232-0.1155-0.0104-0.0798-13.6036-2.403929.664
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|2 - A|165 }A2 - 165
2X-RAY DIFFRACTION2{ B|2 - B|165 }B2 - 165
3X-RAY DIFFRACTION3{ C|2 - C|165 }C2 - 165
4X-RAY DIFFRACTION4{ D|2 - D|165 }D2 - 165
5X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }A201 - 202
6X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }C201
7X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }B201 - 202
8X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }E1 - 11
9X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }D201
10X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }G1 - 11
11X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }F1 - 11
12X-RAY DIFFRACTION5{ A|201 - A|202 C|201 - C|201 B|201 - B|202 E|1 - E|11 D|201 - D|201 G|1 - G|11 F|1 - F|11 H|1 - H|11 }H1 - 11

+
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