Steve Ealick's Research Group


Solanum tuberosum (potato) S-adenosylmethionine decarboxylase


PDB file:

1MHM

Description:

S-adenosylmethionine decarboxylase (AdoMetDC) is a highly regulated enzyme in the polyamine biosynthetic pathway. Because of its importance in cell growth and differentiation, it is a promising target for therapeutic agents against cancer and other proliferative disorders as well as for parasitic diseases. AdoMetDC undergoes an autocatalytic reaction to generate an active site pyruvoyl group before it becomes active for decaryboxylation. Both autocatalysis and decarboxylation are stimulated by putrescine binding to the human enzyme, while AdoMetDC from the potato is not stimulated. The structure of the potato enzyme shows that several amino acid changes relative to human AdoMetDC effectively lock the protein in the stimulated form permanently, eliminating the need for putrescine binding.

Potato AdoMetDC is monomeric in its active form. The monomer has the same four layer α/β fold as the dimeric human AdoMetDC, with two central 8-strand β-sheets flanked on either side by total of seven α- and four 310-helices.


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Because no ligand was present in the active site and because the important residue Phe11 was disordered, the human AdoMetDC/MAOEA complex (pdb 1I72) was used to model the positions of Phe11 and suicide inhibitor MAOEA into the potato enzyme active site. Atoms in crystallographically determined positions are drawn as thick tubes, atoms in the crystal structure that were allowed to move during molecular mechanics modeling are drawn in ball-and-stick representation, and atoms based solely on modeling are shown as thin lines. Carbon atoms are shown in green (except MAOEA carbon atoms, shown in black), oxygen atoms in red, nitrogen atoms in blue, and the sulfur atom in yellow.

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Reference:

Bennett EM, Ekstrom JL, Pegg AE, and Ealick SE. Monomeric S-Adenosylmethionine Decarboxylase from Plants Provides an Alternative to Putrescine Stimulation. Biochemistry 41:14509-14517(2002).



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