Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism

7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg2+-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the Ado Met radical superfamily, which employs the 5'-deoxyadenosyl radical from reductive cleavage of Ado Met 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-45]-bound Ado Met, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg2+, which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the Ado Met radical superfamily in that it contains a hypermodified (beta(6)/alpha(3)) protein core and an expanded cluster-binding motif, CX14CX2C.