Methanogen homoaconitase catalyzes both hydrolyase reactions in coenzyme B biosynthesis

Randy M. Drevland, Yunhua Jia, David R.J. Palmer, David E. Graham

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Homoaconitase enzymes catalyze hydrolyase reactions in the α-aminoadipate pathway for lysine biosynthesis or the 2-oxosuberate pathway for methanogenic coenzyme B biosynthesis. Despite the homology of this iron-sulfur protein to aconitase, previously studied homoaconitases catalyze only the hydration of cis-homoaconitate to form homoisocitrate rather than the complete isomerization of homocitrate to homoisocitrate. The MJ1003 and MJ1271 proteins from the methanogen Methanocaldococcus jannaschii formed the first homoaconitase shown to catalyze both the dehydration of (R)-homocitrate to form cis-homoaconitate, and its hydration is shown to produce homoisocitrate. This heterotetrameric enzyme also used the analogous longer chain substrates cis-(homo)2aconitate, cis-(homo)3aconitate, and cis-(homo) 4aconitate, all with similar specificities. A combination of the homoaconitase with the M. jannaschii homoisocitrate dehydrogenase catalyzed all of the isomerization and oxidative decarboxylation reactions required to form 2-oxoadipate, 2-oxopimelate, and 2-oxosuberate, completing three iterations of the 2-oxoacid elongation pathway. Methanogenic archaeal homoaconitases and fungal homoaconitases evolved in parallel in the aconitase superfamily. The archaeal homoaconitases share a common ancestor with isopropylmalate isomerases, and both enzymes catalyzed the hydration of the minimal substrate maleate to form D-malate. The variation in substrate specificity among these enzymes correlated with the amino acid sequences of a flexible loop in the small subunits.

Original languageEnglish
Pages (from-to)28888-28896
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number43
DOIs
StatePublished - Oct 24 2008
Externally publishedYes

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