[English] 日本語
Yorodumi
- PDB-1m63: Crystal structure of calcineurin-cyclophilin-cyclosporin shows co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1m63
TitleCrystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes
Components
  • CALCINEURIN B SUBUNIT ISOFORM 1
  • CYCLOSPORIN A
  • PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A
  • SERINE/THREONINE PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT, ALPHA ISOFORM
KeywordsHYDROLASE/ISOMERASE/IMMUNOSUPPRESSANT / HYDROLASE-ISOMERASE-IMMUNOSUPPRESSANT COMPLEX / IMMUNOPHILIN / CALCINEURIN / CYCLOSPORIN A / IMMUNOSUPPRESSANT / CYCLOPHILIN
Function / homology
Function and homology information


negative regulation of angiotensin-activated signaling pathway / calcium-dependent protein serine/threonine phosphatase regulator activity / regulation of cell proliferation involved in kidney morphogenesis / positive regulation of glomerulus development / negative regulation of calcium ion import across plasma membrane / negative regulation of signaling / calcium-dependent protein serine/threonine phosphatase activity / positive regulation of saliva secretion / calcineurin complex / positive regulation of connective tissue replacement ...negative regulation of angiotensin-activated signaling pathway / calcium-dependent protein serine/threonine phosphatase regulator activity / regulation of cell proliferation involved in kidney morphogenesis / positive regulation of glomerulus development / negative regulation of calcium ion import across plasma membrane / negative regulation of signaling / calcium-dependent protein serine/threonine phosphatase activity / positive regulation of saliva secretion / calcineurin complex / positive regulation of connective tissue replacement / positive regulation of calcium ion import across plasma membrane / positive regulation of calcium ion-dependent exocytosis of neurotransmitter / positive regulation of cardiac muscle hypertrophy in response to stress / negative regulation of dendrite morphogenesis / protein serine/threonine phosphatase complex / peptidyl-serine dephosphorylation / renal filtration / lung epithelial cell differentiation / calcineurin-NFAT signaling cascade / calmodulin-dependent protein phosphatase activity / skeletal muscle tissue regeneration / positive regulation of calcineurin-NFAT signaling cascade / myelination in peripheral nervous system / negative regulation of protein K48-linked ubiquitination / regulation of apoptotic signaling pathway / cell adhesion molecule production / lipid droplet organization / transition between fast and slow fiber / negative regulation of viral life cycle / heparan sulfate binding / regulation of viral genome replication / positive regulation of osteoclast differentiation / cardiac muscle hypertrophy in response to stress / virion binding / regulation of synaptic vesicle cycle / leukocyte chemotaxis / dephosphorylation / negative regulation of stress-activated MAPK cascade / endothelial cell activation / protein peptidyl-prolyl isomerization / Basigin interactions / extrinsic component of plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / cyclosporin A binding / branching involved in blood vessel morphogenesis / dendrite morphogenesis / Minus-strand DNA synthesis / Plus-strand DNA synthesis / protein-serine/threonine phosphatase / Uncoating of the HIV Virion / regulation of postsynaptic neurotransmitter receptor internalization / parallel fiber to Purkinje cell synapse / Early Phase of HIV Life Cycle / calcineurin-mediated signaling / protein serine/threonine phosphatase activity / Integration of provirus / negative regulation of protein phosphorylation / APOBEC3G mediated resistance to HIV-1 infection / positive regulation of activated T cell proliferation / viral release from host cell / positive regulation of endocytosis / Calcineurin activates NFAT / DARPP-32 events / epithelial to mesenchymal transition / epidermis development / Activation of BAD and translocation to mitochondria / activation of protein kinase B activity / Binding and entry of HIV virion / postsynaptic modulation of chemical synaptic transmission / multicellular organismal response to stress / positive regulation of osteoblast differentiation / phosphatase binding / positive regulation of viral genome replication / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / protein dephosphorylation / skeletal muscle fiber development / keratinocyte differentiation / negative regulation of protein kinase activity / neutrophil chemotaxis / FCERI mediated Ca+2 mobilization / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / positive regulation of cell adhesion / T cell activation / hippocampal mossy fiber to CA3 synapse / Assembly Of The HIV Virion / excitatory postsynaptic potential / positive regulation of protein secretion / Budding and maturation of HIV virion / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / wound healing / G1/S transition of mitotic cell cycle / sarcolemma / positive regulation of NF-kappaB transcription factor activity / modulation of chemical synaptic transmission / platelet activation / platelet aggregation / SARS-CoV-1 activates/modulates innate immune responses
Similarity search - Function
PP2B, metallophosphatase domain / PP2B / Serine/threonine specific protein phosphatases signature. / Protein phosphatase 2A homologues, catalytic domain. / Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase / Cyclophilin-like / Cyclophilin / Metallo-dependent phosphatases / Purple Acid Phosphatase; chain A, domain 2 / Cyclophilin-type peptidyl-prolyl cis-trans isomerase ...PP2B, metallophosphatase domain / PP2B / Serine/threonine specific protein phosphatases signature. / Protein phosphatase 2A homologues, catalytic domain. / Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase / Cyclophilin-like / Cyclophilin / Metallo-dependent phosphatases / Purple Acid Phosphatase; chain A, domain 2 / Cyclophilin-type peptidyl-prolyl cis-trans isomerase / Calcineurin-like phosphoesterase domain, ApaH type / Calcineurin-like phosphoesterase / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site / Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature. / Metallo-dependent phosphatase-like / 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 / EF-hand / Recoverin; domain 1 / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / 4-Layer Sandwich / EF-hand domain pair / Beta Barrel / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Cyclosporin A / : / : / Peptidyl-prolyl cis-trans isomerase A / Calcineurin subunit B type 1 / Protein phosphatase 3 catalytic subunit alpha
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
TOLYPOCLADIUM INFLATUM (fungus)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsHuai, Q. / Kim, H.-Y. / Liu, Y. / Zhao, Y. / Mondragon, A. / Liu, J.O. / Ke, H.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2002
Title: Crystal Structure of Calcineurin-Cyclophilin-Cyclosporin Shows Common But Distinct Recognition of Immunophilin-Drug Complexes
Authors: Huai, Q. / Kim, H.-Y. / Liu, Y. / Zhao, Y. / Mondragon, A. / Liu, J.O. / Ke, H.
History
DepositionJul 12, 2002Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 25, 2002Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Jul 27, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary
Revision 1.4Dec 12, 2012Group: Other
Revision 1.5Nov 1, 2017Group: Derived calculations / Category: pdbx_struct_assembly / Item: _pdbx_struct_assembly.method_details
Revision 1.6Jul 21, 2021Group: Data collection / Derived calculations / Refinement description
Category: pdbx_struct_conn_angle / refine ...pdbx_struct_conn_angle / refine / struct_biol / struct_conn / struct_conn_type / struct_site
Item: _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id ..._pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_comp_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_atom_id / _pdbx_struct_conn_angle.ptnr2_label_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _refine.ls_percent_reflns_obs / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn_type.id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.7Apr 3, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: SERINE/THREONINE PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT, ALPHA ISOFORM
B: CALCINEURIN B SUBUNIT ISOFORM 1
C: PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A
D: CYCLOSPORIN A
E: SERINE/THREONINE PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT, ALPHA ISOFORM
F: CALCINEURIN B SUBUNIT ISOFORM 1
G: PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A
H: CYCLOSPORIN A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)163,21320
Polymers162,6508
Non-polymers56312
Water00
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area17630 Å2
ΔGint-270 kcal/mol
Surface area58150 Å2
MethodPISA
Unit cell
Length a, b, c (Å)108.657, 108.657, 316.590
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212
DetailsOne complex of CN-CyPA-CsA is a biological unit

-
Components

-
Protein , 3 types, 6 molecules AEBFCG

#1: Protein SERINE/THREONINE PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT, ALPHA ISOFORM / CALMODULIN-DEPENDENT CALINEURIN A SUBUNIT / ALPHA ISOFORM / CAM-PRP SUBUNIT


Mass: 42876.148 Da / Num. of mol.: 2 / Fragment: RESIDUES 1-372
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Gene: CNA ALPHA / Plasmid: PET-CNA / Production host: ESCHERICHIA COLI BL21 (bacteria) / Strain (production host): BL21
References: UniProt: Q08209, protein-serine/threonine phosphatase
#2: Protein CALCINEURIN B SUBUNIT ISOFORM 1 / PROTEIN PHOSPHATASE 2B REGULATORY SUBUNIT 1 / PROTEIN PHOSPHATASE 3 REGULATORY SUBUNIT B ALPHA ISOFORM 1


Mass: 19191.709 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Gene: CNB / Plasmid: PET-CNA / Production host: ESCHERICHIA COLI BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: P63098
#3: Protein PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A / PPIASE / ROTAMASE / CYCLOPHILIN A / CYCLOSPORIN A- BINDING PROTEIN


Mass: 18036.504 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PGEX-GST-CYPA / Production host: ESCHERICHIA COLI BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: P62937, peptidylprolyl isomerase

-
Protein/peptide , 1 types, 2 molecules DH

#4: Protein/peptide CYCLOSPORIN A / CYCLOSPORINE / CICLOSPORIN / CICLOSPORINE


Type: Cyclic peptide / Class: Immunosuppressant / Mass: 1220.625 Da / Num. of mol.: 2 / Source method: obtained synthetically
Details: CYCLOSPORIN IS A CYCLIC UNDECAPEPTIDE. CYCLIZATION IS ACHIEVED BY LINKING THE N- AND THE C- TERMINI.
Source: (synth.) TOLYPOCLADIUM INFLATUM (fungus) / References: NOR: NOR00033, Cyclosporin A

-
Non-polymers , 3 types, 12 molecules

#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#6: Chemical ChemComp-FE / FE (III) ION


Mass: 55.845 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Fe
#7: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Ca

-
Details

Compound detailsCYCLOSPORIN IS A CYCLIC UNDECAPEPTIDE. HERE, CYCLOSPORIN A IS REPRESENTED BY THE SEQUENCE (SEQRES)

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.87 Å3/Da / Density % sol: 57.16 %
Crystal growpH: 6.5
Details: 0.1 M NA CACODYLATE, 0.2 M MGCL2, 13% PEG8000, 2.5% ETHANOL, PH 6.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 295K
Crystal grow
*PLUS
pH: 7.5 / Method: vapor diffusion
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDChemical formulaDetails
115 mg/mlprotein1drop
20.1 M1dropNaCl
320 mMTris-HCl1droppH7.5
41 mM2-mercaptoethanol1drop
52 mM1dropCaCl2
60.1 MHEPES1reservoirpH7.5
71.5 M1reservoirLi2SO4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 14-BM-C / Wavelength: 1
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Jun 15, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→40 Å / Num. obs: 43551 / % possible obs: 90.9 % / Observed criterion σ(I): -3 / Redundancy: 4.2 % / Rmerge(I) obs: 0.136 / Rsym value: 0.136 / Net I/σ(I): 7.1
Reflection shellResolution: 2.8→2.9 Å / Rmerge(I) obs: 0.326 / Mean I/σ(I) obs: 1.5 / % possible all: 62.9
Reflection
*PLUS
Highest resolution: 2.8 Å / Num. measured all: 183803 / Rmerge(I) obs: 0.136
Reflection shell
*PLUS
% possible obs: 62.9 % / Rmerge(I) obs: 0.326

-
Processing

Software
NameClassification
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: CNA FROM THE CN-FKBP COMPLEX CYPA FROM THE UNLIGATED STRUCTURE

Resolution: 2.8→40 Å / σ(F): 0 / Stereochemistry target values: ENGH & HUBER
RfactorNum. reflection% reflectionSelection details
Rfree0.322 4151 -10
Rwork0.26 ---
obs0.26 42237 90 %-
Displacement parametersBiso mean: 64.3 Å2
Refinement stepCycle: LAST / Resolution: 2.8→40 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms11173 0 12 0 11185
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONr_bond_refined_d0.013
X-RAY DIFFRACTIONr_angle_refined_deg1.67
Refinement
*PLUS
Highest resolution: 2.8 Å / Lowest resolution: 50 Å / Num. reflection obs: 42377 / Rfactor Rfree: 0.322 / Rfactor Rwork: 0.26
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.013
X-RAY DIFFRACTIONx_angle_d
X-RAY DIFFRACTIONx_angle_deg1.67

+
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