Structural insights into the function of the nicotinate mononucleotide:phenol/p-cresol phosphoribosyltransferase (ArsAB) enzyme from Sporomusa ovata

Sean A. Newmister, Chi Ho Chan, Jorge C. Escalante-Semerena, Ivan Rayment

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Cobamides (Cbas) are cobalt (Co) containing tetrapyrrole-derivatives involved in enzyme-catalyzed carbon skeleton rearrangements, methyl-group transfers, and reductive dehalogenation. The biosynthesis of cobamides is complex and is only performed by some bacteria and achaea. Cobamides have an upper (Coβ) ligand (5′-deoxyadenosyl or methyl) and a lower (Coα) ligand base that contribute to the axial Co coordinations. The identity of the lower Coα ligand varies depending on the organism synthesizing the Cbas. The homoacetogenic bacterium Sporomusa ovata synthesizes two unique phenolic cobamides (i.e., Coα-(phenolyl/p-cresolyl)cobamide), which are used in the catabolism of methanol and 3,4-dimethoxybenzoate by this bacterium. The S. ovata ArsAB enzyme activates a phenolic lower ligand prior to its incorporation into the cobamide. ArsAB consists of two subunits, both of which are homologous (∼35% identity) to the well-characterized Salmonella enterica CobT enzyme, which transfers nitrogenous bases such as 5,6-dimethylbenzimidazole (DMB) and adenine, but cannot utilize phenolics. Here we report the three-dimensional structure of ArsAB, which shows that the enzyme forms a pseudosymmetric heterodimer, provide evidence that only the ArsA subunit has base:phosphoribosyl-transferase activity, and propose a mechanism by which phenolic transfer is facilitated by an activated water molecule.

Original languageEnglish (US)
Pages (from-to)8571-8582
Number of pages12
JournalBiochemistry
Volume51
Issue number43
DOIs
StatePublished - Oct 30 2012

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