Overview for MACiE Entry M0211
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).
Display structure information
Overall Comment: Whilst the PDB code for this entry code cites the EC number as 184.108.40.206, 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 220.127.116.11. The EC number 18.104.22.168 has two distinct classes of reaction (and CATH code) associated with it, those that catalyse the the reduction of 6,7-dihydropteridine (22.214.171.1240), and those that catalyse the reduction of a broad range of nitroaromatic substrates and (more rapidly) quinones (126.96.36.199). 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 1||NAD initiates an elimination of a hydride ion, which attacks the FMN in a nucleophilic addition.|
|Step 2||FMN eliminates the hydride, which attacks the nitro group of the substrate in a nucleophilic addition. The intermediate then deprotonates a water molecule.|
|Step 3||The intermediate eliminates water from itself, forming a nitroso intermediate.|
|Step 4||NAD initiates an elimination of a hydride ion, which attacks the FMN in a nucleophilic addition.|
|Step 5||FMN 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
||Location of Function
Organic Cofactors for M0211
- 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.
- 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.
- 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.
- 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.
Homologue information for M0211 (1idt)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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