5TH5

Crystal Structure of QueE from Bacillus subtilis with 6-carboxypterin-5'-deoxyadenosyl ester bound

Summary for 5TH5

• Entry DOI: 10.2210/pdb5th5/pdb
• Related: 5TGS
• Descriptor: 7-carboxy-7-deazaguanine synthase, IRON/SULFUR CLUSTER, 5'-O-(2-amino-4-oxo-1,4-dihydropteridine-6-carbonyl)adenosine, ... (5 entities in total)
• Functional Keywords: s-adenosylmethionine radical enzyme, 7-carboxy-7-deazaguanine synthase, lyase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 4
• Total formula weight: 121122.14

Authors

Grell, T.A.J.,Dowling, D.P.,Drennan, C.L. (deposition date: 2016-09-29, release date: 2017-01-18, Last modification date: 2023-10-04)

Primary citation

Bruender, N.A.,Grell, T.A.,Dowling, D.P.,McCarty, R.M.,Drennan, C.L.,Bandarian, V.
7-Carboxy-7-deazaguanine Synthase: A Radical S-Adenosyl-l-methionine Enzyme with Polar Tendencies.
J. Am. Chem. Soc., 139:1912-1920, 2017

PubMed Abstract: 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 (QueE) catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products. 6-Carboxypterin (6-CP), an oxidized analogue of the natural substrate 6-carboxy-5,6,7,8-tetrahydropterin (CPH), 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 (6-dAP), 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 (6-CP-dAdo 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 nonreducing conditions highlights the ability of radical SAM enzymes to carry out both polar and radical transformations in the same active site.

PubMed: 28045519
DOI: 10.1021/jacs.6b11381

Experimental method

X-RAY DIFFRACTION (2.407 Å)