PDBsum entry 1kqb

Oxidoreductase

PDB id: 1kqb

Contents

Protein chains

216 a.a. *

Ligands

FMN ×4

BEZ ×4

Waters ×439

* Residue conservation analysis

PDB id:

1kqb

Name:

Oxidoreductase

Title:

Structure of nitroreductase from e. Cloacae complex with inhibitor benzoate

Structure:

Oxygen-insensitive NAD(p)h nitroreductase. Chain: a, b, c, d. Engineered: yes

Source:

Enterobacter cloacae. Organism_taxid: 550. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.80Å R-factor: 0.188 R-free: 0.217

Authors:

C.A.Haynes,R.L.Koder,A.F.Miller,D.W.Rodgers

Key ref:

C.A.Haynes et al. (2002). Structures of nitroreductase in three states: effects of inhibitor binding and reduction. J Biol Chem, 277, 11513-11520. PubMed id: 11805110 DOI: 10.1074/jbc.M111334200

Date:

04-Jan-02 Release date: 13-Feb-02

Protein chains

Q01234  (NFSB_ENTCL) -  Oxygen-insensitive NAD(P)H nitroreductase from Enterobacter cloacae

Seq: 217 a.a.

Struc: 216 a.a.

Enzyme reactions

• Enzyme class: E.C.1.-.-.-

DOI no: 10.1074/jbc.M111334200

J Biol Chem 277:11513-11520 (2002)

PubMed id: 11805110

Structures of nitroreductase in three states: effects of inhibitor binding and reduction.

C.A.Haynes, R.L.Koder, A.F.Miller, D.W.Rodgers.

ABSTRACT

The crystal structure of the nitroreductase enzyme from Enterobacter cloacae has been determined for the oxidized form in separate complexes with benzoate and acetate inhibitors and for the two-electron reduced form. Nitroreductase is a member of a group of enzymes that reduce a broad range of nitroaromatic compounds and has potential uses in chemotherapy and bioremediation. The monomers of the nitroreductase dimer adopt an alpha+beta fold and together bind two flavin mononucleotide prosthetic groups at the dimer interface. In the oxidized enzyme, the flavin ring system adopts a strongly bent (16 degrees ) conformation, and the bend increases (25 degrees ) in the reduced form of the enzyme, roughly the conformation predicted for reduced flavin free in solution. Because free oxidized flavin is planar, the induced bend in the oxidized enzyme may favor reduction, and it may also account for the characteristic inability of the enzyme to stabilize the one electron-reduced semiquinone flavin, which is also planar. Both inhibitors bind over the pyrimidine and central rings of the flavin in partially overlapping sites. Comparison of the two inhibitor complexes shows that a portion of helix H6 can flex to accommodate the differently sized inhibitors suggesting a mechanism for accommodating varied substrates.

Selected figure(s)

Figure 1.
Fig. 1. Overview of the nitroreductase fold. a, ribbons diagram of the nitroreductase dimer showing the location of the flavin mononucleotide prosthetic groups (yellow bonds) at the dimer interface. The bound acetate molecule is shown with red bonds. b, topology of nitroreductase. Panel a was prepared with the program RIBBONS (78).

Figure 4.
Fig. 4. Inhibitor binding to nitroreductase. a, binding of acetate over the isoalloxazine ring system; b, binding of benzoate over the isoalloxazine ring system. Averaged omit density for both inhibitors is contoured at three times the r.m.s. deviation of the map.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 11513-11520) copyright 2002.

Figures were selected by an automated process.