1MHM

Crystal structure of S-adenosylmethionine decarboxylase from potato

Summary for 1MHM

• Entry DOI: 10.2210/pdb1mhm/pdb
• Related: 1JEN
• Descriptor: S-adenosylmethionine decarboxylase (3 entities in total)
• Functional Keywords: covalent pyruvoyl group, lyase
• Biological source: Solanum tuberosum (potato); More
• Total number of polymer chains: 2
• Total formula weight: 39769.15

Authors

Bennett, E.M.,Ekstrom, J.L.,Pegg, A.E.,Ealick, S.E. (deposition date: 2002-08-20, release date: 2002-12-11, Last modification date: 2024-11-20)

Primary citation

Bennett, E.M.,Ekstrom, J.L.,Pegg, A.E.,Ealick, S.E.
Monomeric S-Adenosylmethionine Decarboxylase from Plants Provides an Alternative to Putrescine Stimulation
Biochemistry, 41:14509-14517, 2002

PubMed Abstract: S-Adenosylmethionine decarboxylase has been implicated in cell growth and differentiation and is synthesized as a proenzyme, which undergoes autocatalytic cleavage to generate an active site pyruvoyl group. In mammals, S-adenosylmethionine decarboxylase is active as a dimer in which each protomer contains one alpha subunit and one beta subunit. In many higher organisms, autocatalysis and decarboxylation are stimulated by putrescine, which binds in a buried site containing numerous negatively charged residues. In contrast, plant S-adenosylmethionine decarboxylases are fully active in the absence of putrescine, with rapid autocatalysis that is not stimulated by putrescine. We have determined the structure of the S-adenosylmethionine decarboxylase from potato, Solanum tuberosum, to 2.3 A resolution. Unlike the previously determined human enzyme structure, the potato enzyme is a monomer in the crystal structure. Ultracentrifugation studies show that the potato enzyme is also a monomer under physiological conditions, with a weak self-association constant of 6.5 x 10(4) M(-)(1) for the monomer-dimer association. Although the potato enzyme contains most of the buried charged residues that make up the putrescine binding site in the human enzyme, there is no evidence for a putrescine binding site in the potato enzyme. Instead, several amino acid substitutions, including Leu13/Arg18, Phe111/Arg114, Asp174/Val181, and Phe285/His294 (human/potato), provide side chains that mimic the role of putrescine in the human enzyme. In the potato enzyme, the positively charged residues form an extensive network of hydrogen bonds bridging a cluster of highly conserved negatively charged residues and the active site, including interactions with the catalytic residues Glu16 and His249. The results explain the constitutively high activity of plant S-adenosylmethionine decarboxylases in the absence of putrescine and are consistent with previously proposed models for how putrescine together with the buried, negatively charged site regulates enzyme activity.

PubMed: 12463749
DOI: 10.1021/bi026710u

Experimental method

X-RAY DIFFRACTION (2.3 Å)