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A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited

Authors
  • Bridwell-Rabb, Jennifer
  • Grell, Tsehai A.J.
  • Drennan, Catherine L.
Type
Published Article
Journal
Annual Review of Biochemistry
Publisher
Annual Reviews
Publication Date
Jun 20, 2018
Volume
87
Pages
555–584
Identifiers
DOI: 10.1146/annurev-biochem-062917-012500
Source
Annual Reviews
Keywords
License
Yellow

Abstract

S-adenosylmethionine (AdoMet) has been referred to as both “a poor man's adenosylcobalamin (AdoCbl)” and “a rich man's AdoCbl,” but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.

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