Research Group Dr. Ulrich Ermler

Research Group Dr. Ulrich Ermler

Project Group of Department of Molecular Membrane Biology (MMB)

Our research is focussed on structure biological subjects and for structure determination we use the method of X-ray crystallography. Our major biological interest is directed to enzymes catalyzing biological degradation processes such as the methanogenic pathway (in collaboration with R.K.Thauer and S. Shima, MPI for Terrestrial Microbiology, Marburg), as the dissimilatory sulfate reduction (P.M.H. Kroneck, University Konstanz), and as the cleavage of compounds with inert C-C and C-H bonds predominantly under anaerobic conditions (M. Boll, University Leipzig; G. Fuchs, Universität Freiburg, J. Heider, Universität Marburg; P.M.H. Kroneck). Furthermore, we are, in general, interested on the structure (conformation) of organic or metallic coenzymes, their interactions to the polypeptide chain and their impact on the mechanism of function of the considered protein.

Structure and mechanism of enzymes of methanogenic pathway

Methanogenesis or biogenic methane formation is the final process of the anaerobic food web where consortia of microorganism degrade organic material to the catabolic end product methane. This ancient energy-conserving biological process proceeds under strictly anaerobic conditions and is carried out by a special group of archaeal microorganisms, the methanogens. These microbes are highly specialized with respect to the substrates used: H2 plus CO2, acetate, and a few one-carbon compounds like formate, methanol, methylamines and methylthiols. The biochemical strategy of methanogenesis is to reduce stepwise coenyzme bound and activated C1 intermediates. Specific one-carbon carriers (methanofuran (MFR), tetrahydromethanopterin (H4MPT) and coenzyme M) and electron donors (coenzyme F420, coenzyme B) are required. Methanogenesis is an exothermic process and the negative free energy is converted to ATP via a chemiosmotic mechanism.

H2/H+ interconversion is catalyzed by hydrogenases which are more efficient catalysts than the platinium compounds industrially used for performing this reaction. Besides the well-characterized [Ni, Fe] and [Fe, Fe] hydrogenases we investigated a third type of hydrogenase on a structural and mechanistic level in cooperation with the groups of S. Shima and R.K. Thauer the [Fe] hydrogenase.  [Fe]-hydrogenase is organized as a homodimer consisting of three globular units and catalyzes the reversible reduction of methenyl- to methylene-H4MPT by oxidizing H2. While the unique cofactor Fe-guanylylpyridinol is embedded into the peripheral unit the substrate binds in a cleft between the globular units. Crystal structure analysis suggests that its active site iron is ligated octahedrally by Cys176-sulfur, one CO, the 2-pyridinol’s nitrogen and the 2-pyridinol’s 6-formylmethyl group in an acyl-iron ligation. One of the unidentified ligation sites contains a CO molecule and the other has then to be the H2 binding site.

Structure and mechanism of enzymes of dissimilatory sulfate reduction

The biogeochemical sulfur cycle comprises reactions between sulfur compounds in the oxidation states +VI to –II, predominantly between sulfate, elemental sulfur, and hydrogen sulfide. Billions of tons of sulfur compounds per year are metabolized by various microbial species for the purpose of energy conservation. In these dissimilatory processes specific microorganisms reduce sulfate to hydrogen sulfide under anoxic conditions, and others oxidize sulfur compounds to sulfate under oxic conditions. The biochemical pathway of dissimilatory sulfate reduction proceeds by activating sulfate to adenosine-5’-phosphosulfate by ATP sulfurylase at the expense of ATP. Subsequently, adenosine-5’-phosphosulfate is hydrolyzed and reduced to sulfite and AMP by adenosine-5’-phosphosulfate reductase, and the generated sulfite is finally reduced to hydrogen sulfide by sulfite reductase.

Dissimilatory sulfite reductase (dSir) catalyzes the six-electron reduction of sulfite to hydrogen sulfide under participation of a unique magnetically coupled siroheme-[4Fe-4S] center. We determined the crystal structure of the enzyme from the sulfate-reducing Archaeon Archaeoglobus fulgidus in cooperation with the group of P.M.H. Kroneck. dSir is organized as a heterotetrameric (ab)2 complex composed of two catalytically independent ab heterodimers. Each ab heterodimer harbors two siroheme-[4Fe-4S] center. Only one of them is catalytically active whereas the access to the second one is blocked by a tryptophan residue. The sulfite is ligated to the siroheme iron by its sulphur and the sulfite oxygens are hydrogen-bonded to Arga98, Arga170, Lysa211 and Lysa213.


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