5th5

Publication Abstract from PubMed

Radical S-adenosyl-L-methionine (SAM) enzymes are widely distributed and catalyze diverse reactions. SAM binds to the unique iron atom of a site-differentiated [4Fe-4S] cluster and is reductively cleaved to generate a 5-deoxyadenosyl radical, which initiates turnover. 7-Carboxy-7-deazaguanine (CDG) synthase catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products. 6-Carboxypterin (6-CP), an oxidized analog of the natural substrate 6-carboxy-5,6,7,8-tetrahydropterin (CPH4), is shown to be an alternate substrate for CDG synthase. Under reducing conditions that would promote the reductive cleavage of SAM, 6-CP is turned over to 6-deoxyadenosylpterin, presumably by radical addition of the 5-deoxyadenosine followed by oxidative decarboxylation to the product. By contrast, in the absence of the strong reductant, dithionite, the carboxylate of 6-CP is esterified to generate 6-carboxypterin-5-deoxyadenosyl ester. Structural studies with 6-CP and SAM also reveal electron density consistent with the ester product being formed in crystallo. The differential reactivity of 6-CP under reducing and non-reducing conditions highlights the ability of radical SAM enzymes to carry out both polar and radical transformations in the same active site. .

7-Carboxy-7-deazaguanine synthase - A radical S-adenosyl-L-methionine enzyme with polar tendencies.,Bruender NA, Grell TA, Dowling DP, McCarty RM, Drennan CL, Bandarian V J Am Chem Soc. 2017 Jan 3. doi: 10.1021/jacs.6b11381. PMID:28045519^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.