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An Unprecedented Ring-Contraction Mechanism in Cobalamin-Dependent Radical S‑Adenosylmethionine Enzymes
journal contribution
posted on 2020-08-07, 15:40 authored by Shuo-Qi Sun, Shi-Lu ChenA unique
member of the family of cobalamin (Cbl)-dependent radical S-adenosylmethionine (SAM) enzymes, OxsB, catalyzes the
ring constriction of deoxyadenosine triphosphate (dATP) to the base
oxetane aldehyde phosphate, a crucial precursor for oxetanocin A (OXT-A),
which is an antitumor, antiviral, and antibacterial compound. This
enzyme reveals a new catalytic function for this big family that is
different from the common methylation. On the basis of density functional
theory calculations, a mechanism has been proposed to mainly include
that the generation of 5′-deoxyadenosine radical, a hydrogen
transfer forming 2′-dATP radical, and a Cbl-catalyzed ring
contraction of the deoxyribose in 2′-dATP radical. The ring
contraction is a concerted rearrangement step accompanied by an electron
transfer from the deoxyribose hydroxyl oxygen to CoIII without
any ring-opening intermediate. CoIICbl has been ruled out
as an active state. Other mechanistic characteristics are also revealed.
This unprecedented non-methylation mechanism provides a new catalytic
repertoire for the family of radical SAM enzymes, representing a new
class of ring-contraction enzymes.
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Co IIICo II Cbldeoxyadenosine triphosphateCbl-catalyzed ring contractionOXT-Atheory calculationselectron transferrearrangement stepnon-methylation mechanismring-contraction enzymesbase oxetane aldehyde phosphatering contractionhydrogen transferdeoxyribose hydroxyl oxygendATPUnprecedented Ring-Contraction Mech...ring constrictionSAM enzymes
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