[MSB][Research][AG Einsle]

Metalloproteins and Membrane Proteins
Oliver Einsle

An estimated 30-40% of all proteins contain metal cofactors with a function in enzymatic catalysis, electron transfer or merely in conveying structural stability. Many of these metalloproteins are phylogenetically ancient and are involved in fundamental biochemical processes such as respiration on oxygen and other terminal electron acceptors, photosynthesis or nitrogen fixation. The growing discipline dealing with the operations and mechanisms of metalloproteins is Bioinorganic Chemistry.

The properties of metal centers in biomolecules are finetuned by the most intricate organic ligands, the proteins themselves, enabling them to catalyze complex chemical reactions with efficiencies that can rarely be matched by industrial chemistry. Structural information of high quality is an essential prerequisite for understanding the properties and the function of metalloproteins. Crystal structures also present a strong foundation for further biochemical, kinetic and spectroscopical analyses and theoretical calculations.

Membrane proteins on the other hand fulfill essential functions in transport, signaling and energy metabolism. Biological processes in living cells are strictly compartmentalized and require controlled tansport of metabolites and nutrients between these compartmets to function properly. Our work on membrane proteins primarily addresses transport proteins and energy-transducing systems that are functionally related to the redox enzymes under investigation.

At present, our work is focussed predominantly around the following topics:

Multiheme c Proteins - Iron-protoporphyrin IX, the heme group, is one of the most abundant metal cofactors in enzymes as well as in electron carriers. Cytochromes c are a family of proteins with a varying number of heme groups attached covalently to the protein chain. Within this large group, our main interest currently lies with Cytochrome c Nitrite Reductase.

As a system consisting of two subunits, NrfA and NrfH, nitrite reductase is the terminal electron acceptor in the anaerobic respiration pathway of dissimilatory nitrate reduction to ammonia (DNRA). Its active site is a five-coordinate heme group with an unusual lysine ligand, and the functional respiratory complex contains a total of 18 heme groups. After solving the structure of the catalytic subunit, NrfA, our main focus has now shifted to the full complex, presumably of stoichiometry NrfH2A2. [more]

Nitrogenase - The reaction of the two-component enzyme system nitrogenase is the predominant source for biologically fixed nitrogen, which is an essential constituent part of all biomolecules. Although structures of both parts of the nitrogenase complex, the Fe protein and the MoFe protein, have been available for many years, their function is still poorly understood.

We have determined structures of the MoFe protein at atomic resolution, i.e. better than 1.2 , that allowed for the identification of a heretofore unobserved central ligand in the active site metal cluster. This discovery potentially has substantial implications for our understanding of the function of the enzyme and we are currently working to clarify the role of this central ligand in the reaction mechanism. [more]

Ammonium Transport - The common product of the reactions of NrfA and Nitrogenase is ammonium, the most reduced modification of nitrogen. Only in this form, nitrogen can be used by living organisms for the synthesis of biomolecules. Uptake of ammonium is mediated by a conserved class of integral membrane

proteins termed Ammonium Transporters (Amt). In mammals, the homologs of Amt are the Rhesus blood-type proteins of erythrocytes. We are studying Amt proteins of the hyper- thermophilic archaeon Archaeoglobus fulgidus in order to understand the functionality and regulation of this important class of proteins. [more]


Our work is funded by:


Deutsche Forschungsgemeinschaft


EMBO Young Investigator Programme


Bundesministerium fr Bildung und Forschung



[disclaimer of liability]