Respiratory-chain NADH dehydrogenase 51 Kd subunit signatures

Respiratory-chain NADH dehydrogenase (EC 1.6.5.3) [1,2] (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase). Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex there is one with a molecular weight of 51 Kd (in mammals), which is the second largest subunit of complex I and is a component of the iron-sulfur (IP) fragment of the enzyme. It seems to bind to NAD, FMN, and a 4Fe-4S cluster.

The 51 Kd subunit is highly similar to [3,4]:

• Subunit α of Alcaligenes eutrophus NAD-reducing hydrogenase (gene hoxF) which also binds to NAD, FMN, and a 4Fe-4S cluster.
• Subunit NQO1 of Paracoccus denitrificans NADH-ubiquinone oxidoreductase.
• Subunit F of Escherichia coli NADH-ubiquinone oxidoreductase (gene nuoF).

The 51 Kd subunit and the bacterial hydrogenase α subunit contains three regions of sequence similarities. The first one most probably corresponds to the NAD-binding site, the second to the FMN-binding site, and the third one, which contains three cysteines, to the iron-sulfur binding region. We have developed signature patterns for the FMN-binding and for the 4Fe-4S binding regions.