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Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate
ACS Chemical Biology
  • V. De Cracy-Lagard
  • G. Phillips
  • L. L. Grochowski
  • B. Yacoubi
  • Francis E. Jenney, Jr., Philadelphia College of Osteopathic Medicine
  • M. W. Adams
  • A. G. Murzin
  • R. H. White
Document Type
Article
Publication Date
1-1-2012
Disciplines
Abstract
C-1 carriers are essential cofactors in all domains of life, and in Archaea, these can be derivatives of tetrahydromethanopterin (H4-MPT) or tetrahydrofolate (H4-folate). Their synthesis requires 6-hydroxymethyl-7,8-dihydropterin diphosphate (6-HMDP) as the precursor, but the nature of pathways that lead to its formation were unknown until the recent discovery of the GTP cyclohydrolase IB/MptA family that catalyzes the first step, the conversion of GTP to dihydroneopterin 2′,3′-cyclic phosphate or 7,8-dihydroneopterin triphosphate [El Yacoubi, B.; et al. (2006) J. Biol. Chem., 281, 37586-37593 and Grochowski, L. L.; et al. (2007) Biochemistry46, 6658-6667]. Using a combination of comparative genomics analyses, heterologous complementation tests, and in vitro assays, we show that the archaeal protein families COG2098 and COG1634 specify two of the missing 6-HMDP synthesis enzymes. Members of the COG2098 family catalyze the formation of 6-hydroxymethyl-7,8-dihydropterin from 7,8-dihydroneopterin, while members of the COG1634 family catalyze the formation of 6-HMDP from 6-hydroxymethyl-7,8- dihydropterin. The discovery of these missing genes solves a long-standing mystery and provides novel examples of convergent evolutions where proteins of dissimilar architectures perform the same biochemical function. © 2012 American Chemical Society.
Comments

This article was published in ACS Chemical Biology, Volume 7, Issue 11, Pages 1807-1816.

The published version is available at http://dx.doi.org/10.1021/cb300342u.

Copyright © 2012 ACS.

Citation Information
V. De Cracy-Lagard, G. Phillips, L. L. Grochowski, B. Yacoubi, et al.. "Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate" ACS Chemical Biology Vol. 7 Iss. 11 (2012) p. 1807 - 1816
Available at: http://works.bepress.com/francis_jenney/48/