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

Daniel P. Dowling, Nathan A. Bruender, Anthony P. Young, Reid M. McCarty, Vahe Bandarian, Catherine L. Drennan

Research output: Chapter in Book/Report/Conference proceedingChapter

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Title of host publicationNature chemical biology
Pages106-112
Number of pages7
Volume10
Edition2
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

S-Adenosylmethionine
Metals
Enzymes
Burkholderia
Biosynthetic Pathways
Hydrogen
Binding Sites
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Dowling, D. P., Bruender, N. A., Young, A. P., McCarty, R. M., Bandarian, V., & Drennan, C. L. (2014). Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. In Nature chemical biology (2 ed., Vol. 10, pp. 106-112) https://doi.org/10.1038/nchembio.1426

Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. / Dowling, Daniel P.; Bruender, Nathan A.; Young, Anthony P.; McCarty, Reid M.; Bandarian, Vahe; Drennan, Catherine L.

Nature chemical biology. Vol. 10 2. ed. 2014. p. 106-112.

Research output: Chapter in Book/Report/Conference proceedingChapter

Dowling, DP, Bruender, NA, Young, AP, McCarty, RM, Bandarian, V & Drennan, CL 2014, Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. in Nature chemical biology. 2 edn, vol. 10, pp. 106-112. https://doi.org/10.1038/nchembio.1426
Dowling DP, Bruender NA, Young AP, McCarty RM, Bandarian V, Drennan CL. Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. In Nature chemical biology. 2 ed. Vol. 10. 2014. p. 106-112 https://doi.org/10.1038/nchembio.1426
Dowling, Daniel P. ; Bruender, Nathan A. ; Young, Anthony P. ; McCarty, Reid M. ; Bandarian, Vahe ; Drennan, Catherine L. / Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. Nature chemical biology. Vol. 10 2. ed. 2014. pp. 106-112
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