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PDBsum entry 1b1c

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protein ligands metals links
Oxidoreductase PDB id
1b1c
Jmol
Contents
Protein chain
166 a.a. *
Ligands
FMN
Metals
_CA
Waters ×61
* Residue conservation analysis
PDB id:
1b1c
Name: Oxidoreductase
Title: Crystal structure of the fmn-binding domain of human cytochrome p450 reductase at 1.93a resolution
Structure: Protein (NADPH-cytochrome p450 reductase). Chain: a. Fragment: fmn-binding domain. Synonym: p450r-fmn. Ec: 1.6.2.4
Source: Homo sapiens. Human. Organism_taxid: 9606. Plasmid: pmp cloned into pet15b
Resolution:
1.93Å     R-factor:   0.197     R-free:   0.243
Authors: Q.Zhao,S.Modi,G.Smith,M.Paine,P.D.Mcdonagh,C.R.Wolf,D.Tew, L.-Y.Lian,G.C.K.Roberts,H.P.C.Driessen
Key ref:
Q.Zhao et al. (1999). Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. Protein Sci, 8, 298-306. PubMed id: 10048323 DOI: 10.1110/ps.8.2.298
Date:
19-Nov-98     Release date:   24-Nov-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16435  (NCPR_HUMAN) -  NADPH--cytochrome P450 reductase
Seq:
Struc:
 
Seq:
Struc:
677 a.a.
166 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
FMN
Bound ligand (Het Group name = FMN) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1110/ps.8.2.298 Protein Sci 8:298-306 (1999)
PubMed id: 10048323  
 
 
Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.
Q.Zhao, S.Modi, G.Smith, M.Paine, P.D.McDonagh, C.R.Wolf, D.Tew, L.Y.Lian, G.C.Roberts, H.P.Driessen.
 
  ABSTRACT  
 
The crystal structure of the FMN-binding domain of human NADPH-cytochrome P450 reductase (P450R-FMN), a key component in the cytochrome P450 monooxygenase system, has been determined to 1.93 A resolution and shown to be very similar both to the global fold in solution (Barsukov I et al., 1997, J Biomol NMR 10:63-75) and to the corresponding domain in the 2.6 A crystal structure of intact rat P450R (Wang M et al., 1997, Proc Nat Acad Sci USA 94:8411-8416). The crystal structure of P450R-FMN reported here confirms the overall similarity of its alpha-beta-alpha architecture to that of the bacterial flavodoxins, but reveals differences in the position, number, and length of the helices relative to the central beta-sheet. The marked similarity between P450R-FMN and flavodoxins in the interactions between the FMN and the protein, indicate a striking evolutionary conservation of the FMN binding site. The P450R-FMN molecule has an unusual surface charge distribution, leading to a very strong dipole, which may be involved in docking cytochrome P450 into place for electron transfer near the FMN. Several acidic residues near the FMN are identified by mutagenesis experiments to be important for electron transfer to P4502D6 and to cytochrome c, a clear indication of the part of the molecular surface that is likely to be involved in substrate binding. Somewhat different parts are found to be involved in binding cytochrome P450 and cytochrome c.
 
  Selected figure(s)  
 
Figure 5.
Fig. 5. GRASP electrostatic potential surface of P450R-FMN seen approx- imately along the plane of the central b-sheet, perpendicular to the strands, from b2 toward b5. The protein shows distinct regions of positive and negative charge giving rise to a dipole roughly in the plane of the sheet parallel to the strands centred near the centre of gravity pointing from the flaving ring toward helix 2. Selected positively and negatively charged residues are indicated in blue and red, respectively.
 
  The above figure is reprinted by permission from the Protein Society: Protein Sci (1999, 8, 298-306) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
19884324 C.C.Marohnic, S.P.Panda, K.McCammon, J.Rueff, B.S.Masters, and M.Kranendonk (2010).
Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect.
  Drug Metab Dispos, 38, 332-340.  
19858215 J.Ellis, A.Gutierrez, I.L.Barsukov, W.C.Huang, J.G.Grossmann, and G.C.Roberts (2009).
Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle x-ray scattering.
  J Biol Chem, 284, 36628-36637.  
19465766 M.Guelker, L.Stagg, P.Wittung-Stafshede, and Y.Shamoo (2009).
Pseudosymmetry, high copy number and twinning complicate the structure determination of Desulfovibrio desulfuricans (ATCC 29577) flavodoxin.
  Acta Crystallogr D Biol Crystallogr, 65, 523-534.
PDB codes: 3f6r 3f6s
18980384 C.G.Gherasim, U.Zaman, A.Raza, and R.Banerjee (2008).
Impeded electron transfer from a pathogenic FMN domain mutant of methionine synthase reductase and its responsiveness to flavin supplementation.
  Biochemistry, 47, 12515-12522.  
18847185 M.P.Hay, K.O.Hicks, K.Pchalek, H.H.Lee, A.Blaser, F.B.Pruijn, R.F.Anderson, S.S.Shinde, W.R.Wilson, and W.A.Denny (2008).
Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins.
  J Med Chem, 51, 6853-6865.  
18487202 R.P.Ilagan, M.Tiso, D.W.Konas, C.Hemann, D.Durra, R.Hille, and D.J.Stuehr (2008).
Differences in a conformational equilibrium distinguish catalysis by the endothelial and neuronal nitric-oxide synthase flavoproteins.
  J Biol Chem, 283, 19603-19615.  
16283395 M.Fairhead, S.Giannini, E.M.Gillam, and G.Gilardi (2005).
Functional characterisation of an engineered multidomain human P450 2E1 by molecular Lego.
  J Biol Inorg Chem, 10, 842-853.  
11997441 T.H.Bayburt, and S.G.Sligar (2002).
Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks.
  Proc Natl Acad Sci U S A, 99, 6725-6730.  
11329263 A.Gutierrez, L.Y.Lian, C.R.Wolf, N.S.Scrutton, and G.C.Roberts (2001).
Stopped-flow kinetic studies of flavin reduction in human cytochrome P450 reductase and its component domains.
  Biochemistry, 40, 1964-1975.  
11329262 A.W.Munro, M.A.Noble, L.Robledo, S.N.Daff, and S.K.Chapman (2001).
Determination of the redox properties of human NADPH-cytochrome P450 reductase.
  Biochemistry, 40, 1956-1963.  
11123926 A.Gutierrez, O.Doehr, M.Paine, C.R.Wolf, N.S.Scrutton, and G.C.Roberts (2000).
Trp-676 facilitates nicotinamide coenzyme exchange in the reductive half-reaction of human cytochrome P450 reductase: properties of the soluble W676H and W676A mutant reductases.
  Biochemistry, 39, 15990-15999.  
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 codes are shown on the right.