Prokaryotic molybdopterin oxidoreductases signatures

A number of different prokaryotic oxidoreductases that require and bind a molybdopterin cofactor have been shown [1,2,3] to share a number of regions of sequence similarity. These enzymes are:

• Escherichia coli respiratory nitrate reductase (EC 1.7.99.4). This enzyme complex allows the bacteria to use nitrate as an electron acceptor during anaerobic growth. The enzyme is composed of three different chains: α, β and γ. The α chain (gene narG) is the molybdopterin-binding subunit. Escherichia coli encodes for a second, closely related, nitrate reductase complex which also contains a molybdopterin-binding α chain (gene narZ).
• Escherichia coli anaerobic dimethyl sulfoxide reductase (DMSO reductase). DMSO reductase is the terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. DMSO reductase is composed of three chains: A, B and C. The A chain (gene dmsA) binds molybdopterin.
• Escherichia coli biotin sulfoxide reductases (genes bisC and bisZ). This enzyme reduces a spontaneous oxidation product of biotin, BDS, back to biotin. It may serve as a scavenger, allowing the cell to use biotin sulfoxide as a biotin source.
• Methanobacterium formicicum formate dehydrogenase (EC 1.2.1.2). The α chain (gene fdhA) of this dimeric enzyme binds a molybdopterin cofactor.
• Escherichia coli formate dehydrogenases -H (gene fdhF), -N (gene fdnG) and -O (gene fdoG). These enzymes are responsible for the oxidation of formate to carbon dioxide. In addition to molybdopterin, the α (catalytic) subunit also contains an active site, selenocysteine.
• Wolinella succinogenes polysulfide reductase chain. This enzyme is a component of the phosphorylative electron transport system with polysulfide as the terminal acceptor. It is composed of three chains: A, B and C. The A chain (gene psrA) binds molybdopterin.
• Salmonella typhimurium thiosulfate reductase (gene phsA).
• Escherichia coli trimethylamine-N-oxide reductase (EC 1.6.6.9) (gene torA) [4].
• Nitrate reductase (EC 1.7.99.4) from Klebsiella pneumoniae (gene nasA), Alcaligenes eutrophus, Escherichia coli, Rhodobacter sphaeroides, Thiosphaera pantotropha (gene napA), and Synechococcus PCC 7942 (gene narB).

These proteins range from 715 amino acids (fdhF) to 1246 amino acids (narZ) in size.

We derived three signature patterns for these enzymes. The first is based on a conserved region in the N-terminal section and contains two cysteine residues perhaps involved in binding the molybdopterin cofactor. It should be noted that this region is not present in bisC. The second pattern is derived from a conserved region located in the central part of these enzymes.