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PDBsum entry 2bf4

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protein ligands Protein-protein interface(s) links
Reductase PDB id
2bf4
Jmol
Contents
Protein chains
645 a.a. *
Ligands
FAD ×2
FMN ×4
NAP ×2
SO4 ×3
Waters ×151
* Residue conservation analysis
PDB id:
2bf4
Name: Reductase
Title: A second fmn-binding site in yeast NADPH-cytochrome p450 reductase suggests a novel mechanism of electron transfer by diflavin reductases.
Structure: NADPH-cytochrome p450 reductase. Chain: a, b. Synonym: cpr, p450r. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.00Å     R-factor:   0.197     R-free:   0.261
Authors: L.M.Podust,G.I.Lepesheva,Y.Kim,L.V.Yermalitskaya, V.N.Yermalitsky,D.C.Lamb,S.L.Kelly,M.R.Waterman
Key ref:
D.C.Lamb et al. (2006). A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases. Structure, 14, 51-61. PubMed id: 16407065 DOI: 10.1016/j.str.2005.09.015
Date:
03-Dec-04     Release date:   17-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16603  (NCPR_YEAST) -  NADPH--cytochrome P450 reductase
Seq:
Struc:
 
Seq:
Struc:
691 a.a.
645 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.6.2.4  - NADPH--hemoprotein reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NADPH + n oxidized hemoprotein = NADP+ + n reduced hemoprotein
NADPH
+ n oxidized hemoprotein
= NADP(+)
+ n reduced hemoprotein
      Cofactor: FAD; FMN
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
FMN
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   8 terms 
  Biological process     oxidation-reduction process   6 terms 
  Biochemical function     electron carrier activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2005.09.015 Structure 14:51-61 (2006)
PubMed id: 16407065  
 
 
A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases.
D.C.Lamb, Y.Kim, L.V.Yermalitskaya, V.N.Yermalitsky, G.I.Lepesheva, S.L.Kelly, M.R.Waterman, L.M.Podust.
 
  ABSTRACT  
 
NADPH-cytochrome P450 reductase transfers two reducing equivalents derived from a hydride ion of NADPH via FAD and FMN to the large family of microsomal cytochrome P450 monooxygenases in one-electron transfer steps. The mechanism of electron transfer by diflavin reductases remains elusive and controversial. Here, we determined the crystal structure of truncated yeast NADPH-cytochrome P450 reductase, which is functionally active toward its physiological substrate cytochrome P450, and discovered a second FMN binding site at the interface of the connecting and FMN binding domains. The two FMN binding sites have different accessibilities to the bulk solvent and different amino acid environments, suggesting stabilization of different electronic structures of the reduced flavin. Since only one FMN cofactor is required for function, a hypothetical mechanism of electron transfer is discussed that proposes shuttling of a single FMN between these two sites coupled with the transition between two semiquinone forms, neutral (blue) and anionic (red).
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Hypothetical Mechanism of Electron Transfer by P450 Reductases
(A) Single catalytic turnover of yCPR. Neutral semiquinone is shown in blue, and putative anionic semiquinone is shown in red.
(B) Structures of oxidized and semiquinone states of the isoalloxazine system shown with the si side facing the viewer.
 
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 51-61) copyright 2006.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21265736 L.Aigrain, D.Pompon, and G.Truan (2011).
Role of the interface between the FMN and FAD domains in the control of redox potential and electronic transfer of NADPH-cytochrome P450 reductase.
  Biochem J, 435, 197-206.  
19908820 A.Das, and S.G.Sligar (2009).
Modulation of the cytochrome P450 reductase redox potential by the phospholipid bilayer.
  Biochemistry, 48, 12104-12112.  
19171935 D.Hamdane, C.Xia, S.C.Im, H.Zhang, J.J.Kim, and L.Waskell (2009).
Structure and Function of an NADPH-Cytochrome P450 Oxidoreductase in an Open Conformation Capable of Reducing Cytochrome P450.
  J Biol Chem, 284, 11374-11384.
PDB code: 3es9
  19255466 L.Aigrain, D.Pompon, G.Truan, and S.Moréra (2009).
Cloning, purification, crystallization and preliminary X-ray analysis of a chimeric NADPH-cytochrome P450 reductase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 210-212.  
19483672 L.Aigrain, D.Pompon, S.Moréra, and G.Truan (2009).
Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase.
  EMBO Rep, 10, 742-747.
PDB code: 3fjo
18478283 J.E.Mendieta-Wejebe, M.C.Rosales-Hernández, H.Rios, J.Trujillo-Ferrara, G.López-Pérez, F.Tamay-Cach, R.Ramos-Morales, and J.Correa-Basurto (2008).
Comparing the electronic properties and docking calculations of heme derivatives on CYP2B4.
  J Mol Model, 14, 537-545.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.