Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism
Author(s)Bruender, Nathan A; Young, Anthony P; McCarty, Reid M; Bandarian, Vahe; Drennan, Catherine L.; Dowling, Daniel P.; ... Show more Show less
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7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg[superscript 2+]-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5′-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg[superscript 2+], which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified ([β [subscript 6] over α [subscript 3]]) protein core and an expanded cluster-binding motif, CX[subscript 14]CX[subscript 2]C.
DepartmentMassachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry
Nature Chemical Biology
Nature Publishing Group
Dowling, Daniel P, Nathan A Bruender, Anthony P Young, Reid M McCarty, Vahe Bandarian, and Catherine L Drennan. “Radical SAM Enzyme QueE Defines a New Minimal Core Fold and Metal-Dependent Mechanism.” Nat Chem Biol 10, no. 2 (December 22, 2013): 106–112.
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