Malic enzymes signature

Malic enzymes, or malate oxidoreductases, catalyze the oxidative decarboxylation of malate into pyruvate important for a wide range of metabolic pathways. There are three related forms of malic enzyme [1,2,3]:

• NAD-dependent malic enzyme (EC 1.1.1.38), which uses preferentially NAD and has the ability to decarboxylate oxaloacetate (OAA). It is found in bacteria and insects.
• NAD-dependent malic enzyme (EC 1.1.1.39), which uses preferentially NAD and is unable to decarboxylate OAA. It is found in the mitochondrial matrix of plants and is a heterodimer of highly related subunits.
• NADP-dependent malic enzyme (EC 1.1.1.40), which has a preference for NADP and has the ability to decarboxylate OAA. This form has been found in fungi, animals and plants. In mammals, there are two isozymes: one, mitochondrial and the other, cytosolic. Plants also have two isozymes: chloroplastic and cytosolic.

There are two other proteins which are closely structurally related to malic enzymes:

• Escherichia coli protein sfcA, whose function is not yet known but which could be an NAD or NADP-dependent malic enzyme.
• Yeast hypothetical protein YKL029c, a probable malic enzyme.

There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in binding NAD or NADP. The significance of the third one, located in the central part of the enzymes, is not yet known. We selected this region as a signature pattern for these enzymes.