Function

S-adenosylmethionine decarboxylase (AMD) catalyzes the conversion of S-adenosylmethionine (AdoMet) to S-adenosylmethioninamine . AMD is part of the polyamine biosynthesis, in particular in the biosynthesis of spermine and spermidine from putrescine. AMD uses a covalently bound pyruvate as a cofactor. The active AMD is generated by post-translational cleavage of a precursor molecule. The cleavage results in non-identical α and β subunits and the modification of a serine residue to pyruvate[1]. There are 2 classes of AMD. AMD I is found in bacteria and archae, AMD II is found in eukaryotes.

Relevance

Targeting AMD I may represent a promising strategy for pulmonary hypertension therapy[2].

Structural insight

The biological assembly of S-adenosylmethionine decarboxylase is , containing 2 α and 2 β chains. . The cleavage of the precursor molecule occurs at residue [3]. Water molecules are shown as red spheres.

S-adenosylmethionine decarboxylase with cofactor pyruvate complex with AdoMet 3iwc

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3D structures of S-adenosylmethionine decarboxylase3D structures of S-adenosylmethionine decarboxylase

Updated on 13-March-2022

ReferencesReferences

  1. Mad Arif SA, Taylor MA, George LA, Butler AR, Burch LR, Davies HV, Stark MJ, Kumar A. Characterisation of the S-adenosylmethionine decarboxylase (SAMDC) gene of potato. Plant Mol Biol. 1994 Oct;26(1):327-38. PMID:7948879
  2. Weisel FC, Kloepping C, Pichl A, Sydykov A, Kojonazarov B, Wilhelm J, Roth M, Ridge KM, Igarashi K, Nishimura K, Maison W, Wackendorff C, Klepetko W, Jaksch P, Ghofrani HA, Grimminger F, Seeger W, Schermuly RT, Weissmann N, Kwapiszewska G. Impact of S-adenosylmethionine decarboxylase 1 on pulmonary vascular remodeling. Circulation. 2014 Apr 8;129(14):1510-23. doi: 10.1161/CIRCULATIONAHA.113.006402. , Epub 2014 Jan 27. PMID:24470481 doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.113.006402
  3. Bale S, Baba K, McCloskey DE, Pegg AE, Ealick SE. Complexes of Thermotoga maritimaS-adenosylmethionine decarboxylase provide insights into substrate specificity. Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):181-9. Epub 2010, Jan 22. PMID:20124698 doi:10.1107/S090744490904877X

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