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Crystal Structure of QueE from Burkholderia multivorans in complex with AdoMet and 6-carboxy-5,6,7,8-tetrahydropterinCrystal Structure of QueE from Burkholderia multivorans in complex with AdoMet and 6-carboxy-5,6,7,8-tetrahydropterin
Structural highlights
FunctionQUEE_BURM1 Catalyzes the complex heterocyclic radical-mediated conversion of 6-carboxy-5,6,7,8-tetrahydropterin (CPH4) to 7-carboxy-7-deazaguanine (CDG), a step common to the biosynthetic pathways of all 7-deazapurine-containing compounds.[HAMAP-Rule:MF_00917][1] Publication Abstract from PubMed7-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 (beta6/alpha3) protein core and an expanded cluster-binding motif, CX14CX2C. Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism.,Dowling DP, Bruender NA, Young AP, McCarty RM, Bandarian V, Drennan CL Nat Chem Biol. 2014 Feb;10(2):106-12. doi: 10.1038/nchembio.1426. Epub 2013 Dec, 22. PMID:24362703[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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