Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism.
Publication Type:Journal Article
Source:Nat Chem Biol, Volume 10, Issue 2, p.106-12 (2014)
Keywords:Binding Sites, Burkholderia, Free Radicals, Hydrogen Bonding, Magnesium, Manganese, Models, Molecular, Molecular Structure, Protein Structure, Tertiary, S-Adenosylmethionine, Sodium
<p>7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg(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(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 (β6/α3) protein core and an expanded cluster-binding motif, CX14CX2C. </p>