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Overview for MACiE Entry M0211

Version history

General Information

EC Number: 1.7.1.- (A member of the Oxidoreductases, Acting on other nitrogenous compounds as donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: oxygen insensitive NAD(P)H nitroreductase

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P38489 - Oxygen-insensitive NAD(P)H nitroreductase

Representative PDB Code: 1idt - STRUCTURAL STUDIES ON A PRODRUG-ACTIVATING SYSTEM-CB1954AND FMN-DEPENDENT NITROREDUCTASE (Resolution = 2.00 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of proton

Image of NADH

Image of 2-Nitrobenzoate

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Image of NAD+

Image of 2-Hydroxylaminobenzoate

Image of Water

2 proton
C00080
CHEBI:24636
2 NADH
C00004
CHEBI:16908
2-Nitrobenzoate
C16234
CHEBI:25619
2 NAD+
C00003
CHEBI:15846
2-Hydroxylaminobenzoate
C16235
Water
C00001
CHEBI:15377

Overall Comment: Whilst the PDB code for this entry code cites the EC number as 1.5.1.34, upon closer inspection the closest sub-subclass to this mechanism is 1.7.1.-. There is no direct correspondence to this reaction, and so the serial number cannot be assigned correctly, however the closest match is 1.7.1.9. The EC number 1.5.1.34 has two distinct classes of reaction (and CATH code) associated with it, those that catalyse the the reduction of 6,7-dihydropteridine (3.40.50.720), and those that catalyse the reduction of a broad range of nitroaromatic substrates and (more rapidly) quinones (3.40.109.10). This particular case shows the mechanism for the reduction of 2-nitrobenzoate. Escherichia coli nitroreductase a homodimeric enzyme with two active sites that is capable of using either NADH or NADPH as the reducing equivalents and has a substituted enzyme ('ping-pong') bi-bi mechanism.


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Stepwise Description of the Reaction

Step 1NAD initiates an elimination of a hydride ion, which attacks the FMN in a nucleophilic addition.
Step 2FMN eliminates the hydride, which attacks the nitro group of the substrate in a nucleophilic addition. The intermediate then deprotonates a water molecule.
Step 3The intermediate eliminates water from itself, forming a nitroso intermediate.
Step 4NAD initiates an elimination of a hydride ion, which attacks the FMN in a nucleophilic addition.
Step 5FMN eliminates the hydride, which attacks the nitroso group of the intermediate in a nucleophilic addition. The intermediate then deprotonates a water molecule to produce the product.

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Catalytic Residues Involved

Type Number Chain Location of Function
Lys 14 A Side Chain
Lys 74 A Side Chain

Organic Cofactors for M0211

Type Identity Chain
FMN FMN 1218 Overview

References

  1. P. R. Race et al. (2005), J. Biol. Chem., 280, 13256-13264. Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme.
    Medline: 15684426
  2. E. Johansson et al. (2003), J. Med. Chem., 46, 4009-4020. Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form.
    Medline: 12954054
  3. A. L. Lovering et al. (2001), J. Mol. Biol., 309, 203-213. The structure of Escherichia coli nitroreductase complexed with nicotinic acid: three crystal forms at 1.7 A, 1.8 A and 2.4 A resolution.
    Medline: 11491290
  4. G. N. Parkinson et al. (2000), J. Med. Chem., 43, 3624-3631. Crystal structure of FMN-dependent nitroreductase from Escherichia coli B: a prodrug-activating enzyme.
    Medline: 11020276

Homologue information for M0211 (1idt)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

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