5UL3

Structure of Cobalamin-dependent S-adenosylmethionine radical enzyme OxsB with aqua-cobalamin bound

Summary for 5UL3

• Entry DOI: 10.2210/pdb5ul3/pdb
• Related: 5UL2 5UL4
• Descriptor: OxsB protein, IRON/SULFUR CLUSTER, COBALAMIN, ... (7 entities in total)
• Functional Keywords: metalloprotein, cobalamin, radical sam, s-adenosylmethionine, oxetanocin, metal binding protein
• Biological source: Bacillus megaterium
• Total number of polymer chains: 1
• Total formula weight: 90204.50

Authors

Bridwell-Rabb, J.,Drennan, C.L. (deposition date: 2017-01-24, release date: 2017-04-19, Last modification date: 2024-04-03)

Primary citation

Bridwell-Rabb, J.,Zhong, A.,Sun, H.G.,Drennan, C.L.,Liu, H.W.
A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis.
Nature, 544:322-326, 2017

PubMed Abstract: Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'. Hence, OxsB represents the first biochemically characterized non-methylating Cbl-dependent AdoMet radical enzyme. X-ray analysis of OxsB reveals the fold of a Cbl-dependent AdoMet radical enzyme, a family of enzymes with an estimated 7,000 members. Overall, this work provides a framework for understanding the interplay of AdoMet and Cbl cofactors and expands the catalytic repertoire of Cbl-dependent AdoMet radical enzymes.

PubMed: 28346939
DOI: 10.1038/nature21689

Experimental method

X-RAY DIFFRACTION (1.8 Å)