The role of the maturase HydG in [FeFe]-hydrogenase active site synthesis and assembly

Pilet, Eric; Nicolet, Yvain; Mathevon, Carole; Douki, Thierry; Fontecilla-Camps, Juan C.; Fontecave, Marc

doi:10.1016/j.febslet.2009.01.004

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Volume 583, Issue 3 , Pages 506-511, 4 February 2009

The role of the maturase HydG in [FeFe]-hydrogenase active site synthesis and assembly

Edited by Hans Eklund

Eric Pilet
- Laboratoire de Chimie et Biologie des Métaux, Université Joseph Fourier, UMR 5249-CNRS, IRTSV/CEA-Grenoble 17 avenue des Martyrs, 38054 Grenoble Cedex, France
Yvain Nicolet
- Laboratoire de Cristallographie et Cristallogenèse des Protéines; Institut de Biologie Structurale J.P. Ebel; CEA; CNRS; Université J. Fourier, 41 rue J. Horowitz, 38027 Grenoble Cedex 1, France
Carole Mathevon
- Laboratoire de Chimie et Biologie des Métaux, Université Joseph Fourier, UMR 5249-CNRS, IRTSV/CEA-Grenoble 17 avenue des Martyrs, 38054 Grenoble Cedex, France
Thierry Douki
- DSM/INAC/SCIB UMR-E3 CEA/UJF/Laboratoire “Lesions des Acides Nucleiques”, CEA-Grenoble, 17 Avenue des Martyrs, F-38054 Grenoble Cedex 9, France
Juan C. Fontecilla-Camps
- Laboratoire de Cristallographie et Cristallogenèse des Protéines; Institut de Biologie Structurale J.P. Ebel; CEA; CNRS; Université J. Fourier, 41 rue J. Horowitz, 38027 Grenoble Cedex 1, France
Marc Fontecave
- Laboratoire de Chimie et Biologie des Métaux, Université Joseph Fourier, UMR 5249-CNRS, IRTSV/CEA-Grenoble 17 avenue des Martyrs, 38054 Grenoble Cedex, France
- Corresponding author. Fax: +33 438789124.

Received 4 December 2008; received in revised form 7 January 2009; accepted 8 January 2009. published online 21 January 2009.

Abstract

[FeFe]-hydrogenases catalyze the protons/hydrogen interconversion through a unique di-iron active site consisting of three CO and two CN ligands, and a non-protein SCH₂XCH₂S (X=N or O) dithiolate bridge. Site assembly requires two “Radical-S-adenosylmethionine (SAM or AdoMet)” iron–sulfur enzymes, HydE and HydG, and one GTPase, HydF. The sequence homology between HydG and ThiH, a Radical-SAM enzyme which cleaves tyrosine into p-cresol and dehydroglycine, and the finding of a similar cleavage reaction catalyzed by HydG suggests a mechanism for hydrogenase maturation. Here we propose that HydG is specifically involved in the synthesis of the dithiolate ligand, with two tyrosine-derived dehydroglycines as precursors along with an [FeS] cluster of HydG functioning both as electron shuttle and source of the sulfur atoms.