Structural biology of S-adenosylmethionine decarboxylase

• Published in: Amino acids Vol. 38; no. 2; pp. 451 - 460
• Main Authors: Bale, Shridhar, Ealick, Steven E
• Format: Journal Article
• Language: English
• Published: Vienna Vienna : Springer Vienna 01.02.2010; Springer Vienna; Springer Nature B.V
• Subjects: active sites; Adenosylmethionine decarboxylase; Adenosylmethionine Decarboxylase - chemistry; Adenosylmethionine Decarboxylase - genetics; Adenosylmethionine Decarboxylase - metabolism; Amino acids; Analytical Chemistry; Animals; Antiparasitic agents; Aquifex; Bacteria - chemistry; Bacteria - enzymology; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biochemical Engineering; biochemical pathways; Biochemistry; Biology; Biomedical and Life Sciences; Catalytic Domain; Crystal structure; Decarboxylation; divergent evolution; Enzymes; Eukaryota - chemistry; Eukaryota - enzymology; Eukaryota - genetics; Evolution; Gene duplication; Gene fusion; Human; Humans; Inhibitors; Life Sciences; Molecular Sequence Data; mutants; Neurobiology; Polyamines; Post-translation; post-translational modification; potatoes; Protein Structure, Secondary; Proteomics; Putrescine; Review Article; S-Adenosylmethionine; Solanum tuberosum; Substrate inhibition; Substrate Specificity; therapeutics; Thermotoga maritima; Protein evolution; Pyruvoyl cofactor; Polyamines; Putrescine activation; Cation–π interactions
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-009-0404-y

S-adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and a subject of many structural and biochemical investigations for anti-cancer and anti-parasitic therapy. The enzyme undergoes an internal serinolysis reaction as a post-translational modification to generate the active site pyruvoyl group for the decarboxylation process. The crystal structures of AdoMetDC from Homo sapiens, Solanum tuberosum, Thermotoga maritima, and Aquifex aeolicus have been determined. Numerous crystal structures of human AdoMetDC and mutants have provided insights into the mechanism of autoprocessing, putrescine activation, substrate specificity, and inhibitor design to the enzyme. The comparison of the human and potato enzyme with the T. maritima and A. aeolicus enzymes supports the hypothesis that the eukaryotic enzymes evolved by gene duplication and fusion. The residues implicated in processing and activity are structurally conserved in all forms of the enzyme, suggesting a divergent evolution of AdoMetDC.