Corrinoid Adenosyltransferases

Paola E. Mera, Ivan Rayment, Jorge C. Escalante-semerena

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

ATP corrinoid adenosyltransferase (ACA) enzymes catalyze the transfer of the adenosyl moiety from ATP to cob(I)alamin, resulting in the formation of the unique organometallic C–Co bond characteristic of coenzyme B12 (adenosylcobalamin, AdoCbl). In the last decade, our knowledge of how these enzymes catalyze the adenosylation of cobalamin has grown rapidly. ACA enzymes also facilitate the thermodynamically unfavorable reduction of cob(II)alamin. Studies with ACA enzymes revealed an unprecedented four‐coordinate square‐planar corrinoid conformation. ACA enzymes bring the reduction potential of cob(II)alamin to within physiological range by generating the four‐coordinate Co(II) corrinoid species. Recently, visual evidence of the existence of a Co(II) corrinoid species was obtained when the 3D crystal structure of the human‐type ACA enzyme was solved with ATP and cob(II)alamin bound in the active site. To date, three types of ACA enzymes have been identified, CobA, PduO, and EutT. The PduO‐type is the most widely distributed ACA enzyme and is the form found in humans where ACA enzymes play an essential role in metabolism; malfunctioning of this enzyme cause severe health defects. Detailed analyses of the catalytic mechanism of ACA enzymes have provided an understanding of how some mutations in the human ACA enzyme render it inactive.
Original languageEnglish (US)
Title of host publicationHandbook of Metalloproteins
EditorsAlbrecht Messerschmidt
PublisherJohn Wiley & Sons, Ltd
ISBN (Electronic)9780470028636
ISBN (Print)9780470869819
DOIs
StatePublished - Dec 15 2009
Externally publishedYes

Keywords

  • corrinoid adenosyltransferases
  • Vitamin B12
  • methylmalonic aciduria
  • coenzyme B12 biosynthesis
  • cobalamin adenosylation
  • organometallic bonds
  • Co–C bond

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