X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry

Peter J. Goldman, Tyler L. Groèe, Squire J. Booker, Catherine L. Drennan

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The 2-deoxy-scyllo-inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S-adenosyl-L-methionine (AdoMet) radical enzyme. To examine how BtrN employs AdoMet radical chemistry, we haèe determined its structure with AdoMet and substrate to 1.56 A resolution. We find a preèiously undescribed modification to the core AdoMet radical fold: instead of the canonical (β/α)6 architecture, BtrN displays a (β5/α4) motif. We further find that an auxiliary [4Fe-4S] cluster in BtrN, thought to bind substrate, is instead implicated in substrate-radical oxidation. High structural homology in the auxiliary cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofactor biosynthetic enzyme MoaA proèides support for the establishment of an AdoMet radical structural motif that is likely common to 6,400 uncharacterized AdoMet radical enzymes.

Original languageEnglish (US)
Pages (from-to)15949-15954
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number40
DOIs
StatePublished - Oct 1 2013

    Fingerprint

All Science Journal Classification (ASJC) codes

  • General

Cite this