4JJM

Structure of a cyclophilin from Citrus sinensis (CsCyp) in complex with cyclosporin A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

A redox 2-cys mechanism regulates the catalytic activity of divergent cyclophilins.

Campos, B.M.Sforca, M.L.Ambrosio, A.L.Domingues, M.N.Brasil de Souza Tde, A.Barbosa, J.A.R.G.Paes Leme, A.F.Perez, C.A.Whittaker, S.B.Murakami, M.T.Zeri, A.C.Benedetti, C.E.

(2013) Plant Physiol 162: 1311-1323

  • DOI: https://doi.org/10.1104/pp.113.218339
  • Primary Citation of Related Structures:  
    4JJM

  • PubMed Abstract: 

    The citrus (Citrus sinensis) cyclophilin CsCyp is a target of the Xanthomonas citri transcription activator-like effector PthA, required to elicit cankers on citrus. CsCyp binds the citrus thioredoxin CsTdx and the carboxyl-terminal domain of RNA polymerase II and is a divergent cyclophilin that carries the additional loop KSGKPLH, invariable cysteine (Cys) residues Cys-40 and Cys-168, and the conserved glutamate (Glu) Glu-83. Despite the suggested roles in ATP and metal binding, the functions of these unique structural elements remain unknown. Here, we show that the conserved Cys residues form a disulfide bond that inactivates the enzyme, whereas Glu-83, which belongs to the catalytic loop and is also critical for enzyme activity, is anchored to the divergent loop to maintain the active site open. In addition, we demonstrate that Cys-40 and Cys-168 are required for the interaction with CsTdx and that CsCyp binds the citrus carboxyl-terminal domain of RNA polymerase II YSPSAP repeat. Our data support a model where formation of the Cys-40-Cys-168 disulfide bond induces a conformational change that disrupts the interaction of the divergent and catalytic loops, via Glu-83, causing the active site to close. This suggests a new type of allosteric regulation in divergent cyclophilins, involving disulfide bond formation and a loop-displacement mechanism.


  • Organizational Affiliation

    Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP CP6192, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase
A, B
175Citrus sinensisMutation(s): 0 
Gene Names: CYP
EC: 5.2.1.8
UniProt
Find proteins for D0ELH5 (Citrus sinensis)
Explore D0ELH5 
Go to UniProtKB:  D0ELH5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupD0ELH5
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
cyclosporin AC [auth E],
D [auth F]
11Tolypocladium inflatumMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  5 Unique
IDChains TypeFormula2D DiagramParent
ABA
Query on ABA
C [auth E],
D [auth F]
L-PEPTIDE LINKINGC4 H9 N O2ALA
BMT
Query on BMT
C [auth E],
D [auth F]
L-PEPTIDE LINKINGC10 H19 N O3THR
MLE
Query on MLE
C [auth E],
D [auth F]
L-PEPTIDE LINKINGC7 H15 N O2LEU
MVA
Query on MVA
C [auth E],
D [auth F]
L-PEPTIDE LINKINGC6 H13 N O2VAL
SAR
Query on SAR
C [auth E],
D [auth F]
PEPTIDE LINKINGC3 H7 N O2GLY
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.63α = 90
b = 83.63β = 90
c = 85.03γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-12
    Type: Initial release
  • Version 1.1: 2013-07-17
    Changes: Database references
  • Version 1.2: 2017-06-21
    Changes: Database references
  • Version 1.3: 2018-12-05
    Changes: Data collection, Structure summary
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.5: 2023-12-06
    Changes: Data collection, Derived calculations