Reaction mechanism of the iron-sulfur flavoenzyme adenosine-5'-phosphosulfate reductase based on the structural characterization of different enzymatic states

Biochemistry
Alexander SchifferUlrich Ermler

Abstract

The iron-sulfur flavoenzyme adenosine-5'-phosphosulfate (APS) reductase catalyzes a key reaction of the global sulfur cycle by reversibly transforming APS to sulfite and AMP. The structures of the dissimilatory enzyme from Archaeoglobus fulgidus in the reduced state (FAD(red)) and in the sulfite adduct state (FAD-sulfite-AMP) have been recently elucidated at 1.6 and 2.5 A resolution, respectively. Here we present new structural features of the enzyme trapped in four different catalytically relevant states that provide us with a detailed picture of its reaction cycle. In the oxidized state (FAD(ox)), the isoalloxazine moiety of the FAD cofactor exhibits a similarly bent conformation as observed in the structure of the reduced enzyme. In the APS-bound state (FAD(ox)-APS), the substrate APS is embedded into a 17 A long substrate channel in such a way that the isoalloxazine ring is pushed toward the channel bottom, thereby producing a compressed enzyme-substrate complex. A clamp formed by residues ArgA317 and LeuA278 to fix the adenine ring and the curved APS conformation appear to be key factors to hold APS in a strained conformation. This energy-rich state is relaxed during the attack of APS on the reduced FAD. A relaxed FAD-sulf...Continue Reading

Citations

Nov 11, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Hideaki OgataWolfgang Lubitz
Dec 6, 2014·Acta Crystallographica. Section D, Biological Crystallography·Emily GoldenAlice Vrielink
Oct 31, 2006·Current Opinion in Structural Biology·Luigi De Colibus, Andrea Mattevi
May 26, 2012·Environmental Microbiology·Yuchen LiuWilliam B Whitman
Apr 8, 2015·Acta Crystallographica. Section D, Biological Crystallography·Ai-Fen ChaiJodie M Johnston
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Sep 14, 2013·Journal of Biomolecular Structure & Dynamics·Elias Silva Dos SantosElias Ramos-de-Souza
Jan 11, 2019·Nature Communications·Min Sub SimShawn E McGlynn
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Feb 17, 2007·Science·Takaaki SatoTadayuki Imanaka

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