PDBsum entry 1b1c

Oxidoreductase

PDB id: 1b1c

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

Protein chain

P16435  (NCPR_HUMAN) -  NADPH--cytochrome P450 reductase from Homo sapiens

Seq: 677 a.a.

Struc: 166 a.a.

Enzyme reactions

• Enzyme class: E.C.1.6.2.4 - NADPH--hemoprotein reductase.
• Reaction: 2 oxidized [cytochrome P450] + NADPH = 2 reduced [cytochrome P450] + NADP⁺ + H⁺
• 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

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.