3MVR

Crystal Structure of cytochrome P450 2B4-H226Y in a closed conformation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

Plasticity of Cytochrome P450 2B4 as Investigated by Hydrogen-Deuterium Exchange Mass Spectrometry and X-ray Crystallography.

Wilderman, P.R.Shah, M.B.Liu, T.Li, S.Hsu, S.Roberts, A.G.Goodlett, D.R.Zhang, Q.Woods, V.L.Stout, C.D.Halpert, J.R.

(2010) J Biol Chem 285: 38602-38611

  • DOI: https://doi.org/10.1074/jbc.M110.180646
  • Primary Citation of Related Structures:  
    3MVR

  • PubMed Abstract: 

    Crystal structures of the xenobiotic metabolizing cytochrome P450 2B4 have demonstrated markedly different conformations in the presence of imidazole inhibitors or in the absence of ligand. However, knowledge of the plasticity of the enzyme in solution has remained scant. Thus, hydrogen-deuterium exchange mass spectrometry (DXMS) was utilized to probe the conformations of ligand-free P450 2B4 and the complex with 4-(4-chlorophenyl)imidazole (4-CPI) or 1-biphenyl-4-methyl-1H-imidazole (1-PBI). The results of DXMS indicate that the binding of 4-CPI slowed the hydrogen-deuterium exchange rate over the B'- and C-helices and portions of the F-G-helix cassette compared with P450 2B4 in the absence of ligands. In contrast, there was little difference between the ligand-free and 1-PBI-bound exchange sets. In addition, DXMS suggests that the ligand-free P450 2B4 is predominantly open in solution. Interestingly, a new high resolution structure of ligand-free P450 2B4 was obtained in a closed conformation very similar to the 4-CPI complex. Molecular dynamics simulations performed with the closed ligand-free structure as the starting point were used to probe the energetically accessible conformations of P450 2B4. The simulations were found to equilibrate to a conformation resembling the 1-PBI-bound P450 2B4 crystal structure. The results indicate that conformational changes observed in available crystal structures of the promiscuous xenobiotic metabolizing cytochrome P450 2B4 are consistent with its solution structural behavior.


  • Organizational Affiliation

    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytochrome P450 2B4
A, B
476Oryctolagus cuniculusMutation(s): 9 
Gene Names: CYP2B4
EC: 1.14.14.1
UniProt
Find proteins for P00178 (Oryctolagus cuniculus)
Explore P00178 
Go to UniProtKB:  P00178
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00178
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: P 31
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.47α = 90
b = 91.47β = 90
c = 150.4γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
iMOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-01-24
    Changes: Database references
  • Version 1.3: 2021-10-06
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description