Elmar Jaenicke
University of Mainz
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Elmar Jaenicke.
Integrative and Comparative Biology | 2007
Heinz Decker; Nadja Hellmann; Elmar Jaenicke; Bernhard Lieb; Ulrich Meissner; Jürgen Markl
This review summarizes recent highlights of our joint work on the structure, evolution, and function of a family of highly complex proteins, the hemocyanins. They are blue-pigmented oxygen carriers, occurring freely dissolved in the hemolymph of many arthropods and molluscs. They are copper type-3 proteins and bind one dioxygen molecule between two copper atoms in a side-on coordination. They possess between 6 and 160 oxygen-binding sites, and some of them display the highest molecular cooperativity observed in nature. The functional properties of hemocyanins can be convincingly described by either the Monod-Wyman-Changeux (MWC) model or its hierarchical extension, the Nested MWC model; the latter takes into account the structural hierarchies in the oligomeric architecture. Recently, we applied these models to interpret the influence of allosteric effectors in detailed terms. Effectors shift the allosteric equilibria but have no influence on the oxygen affinities characterizing the various conformational states. We have shown that hemocyanins from species living at different environmental temperatures have a cooperativity optimum at the typical temperature of their natural habitat. Besides being oxygen carriers, some hemocyanins function as a phenoloxidase (tyrosinase/catecholoxidase) which, however, requires activation. Chelicerates such as spiders and scorpions lack a specific phenoloxidase, and in these animals activated hemocyanin might catalyse melanin synthesis in vivo. We propose a similar activation mechanism for arthropod hemocyanins, molluscan hemocyanins and tyrosinases: amino acid(s) that sterically block the access of phenolic compounds to the active site have to be removed. The catalysis mechanism itself can now be explained on the basis of the recently published crystal structure of a tyrosinase. In a series of recent publications, we presented the complete gene and primary structure of various hemocyanins from different molluscan classes. From these data, we deduced that the molluscan hemocyanin molecule evolved ca. 740 million years ago, prior to the separation of the extant molluscan classes. Our recent advances in the 3D cryo-electron microscopy of hemocyanins also allow considerable insight into the oligomeric architecture of these proteins of high molecular mass. In the case of molluscan hemocyanin, the structure of the wall and collar of the basic decamers is now rapidly becoming known in greater detail. In the case of arthropod hemocyanin, a 10-Å structure and molecular model of the Limulus 8 × 6mer shows the amino acids at the various interfaces between the eight hexamers, and reveals histidine-rich residue clusters that might be involved in transferring the conformational signals establishing cooperative oxygen binding.
Biochemical Journal | 2003
Elmar Jaenicke; Heinz Decker
Tyrosinases, which are widely distributed among animals, plants and fungi, are involved in many biologically essential functions, including pigmentation, sclerotization, primary immune response and host defence. In the present study, we present a structural and physicochemical characterization of two new tyrosinases from the crustaceans Palinurus elephas (European spiny lobster) and Astacus leptodactylus (freshwater crayfish). In vivo, the purified crustacean tyrosinases occur as hexamers composed of one subunit type with a molecular mass of approx. 71 kDa. The tyrosinase hexamers appear to be similar to the haemocyanins, based on electron microscopy. Thus a careful purification protocol was developed to discriminate clearly between tyrosinases and the closely related haemocyanins. The physicochemical properties of haemocyanins and tyrosinases are different with respect to electronegativity and hydrophobicity. The hexameric nature of arthropod tyrosinases suggests that these proteins were the ideal predecessors from which to develop the oxygen-carrier protein haemocyanin, with its allosteric and co-operative properties, later on.
ChemBioChem | 2004
Elmar Jaenicke; Heinz Decker
When life developed on earth, it happened in a reducing atmosphere where oxygen was only a trace element. Thus, the first cells and organisms produced metabolites necessary for life under anaerobic conditions. Some 3500 million years ago some bacteria began to meet their energy needs by photosynthesis. Dioxygen as well as its highly reactive derivatives, hydrogen peroxide, superoxide anions, and hydroxyl radicals, were released as by-products and became a severe poison for the hitherto anaerobic cells. To cope with these highly reactive oxygen species and minimize the damage caused by them, different kinds of enzymes emerged. These enzymes, such as superoxide dismutase, catalase, peroxidase, monooxygenases, and dioxygenases, react with oxygen to yield harmless end products. Many of these enzymes, such as tyrosinase (EC 1.14.18.1), incorporate oxygen into organic compounds by hydroxylation. This enzyme catalyzes two reactions, the hydroxylation of phenolic compounds in the ortho position (cresolase activity) and subsequently oxidation of diphenolic products (catecholase activity). Tyrosinase as well as catecholoxidase (EC 1.10.3.1), which catalyzes only the oxidation, belong to the group termed phenoloxidases. Their presence in all phyla of living organisms demonstrates their early origin in the history of life. Tyrosinases and catecholoxidases bind oxygen at copper-containing active sites, called type 3 copper sites. This distinction was originally based on their specific EPR spectra. 5] Their active site is a binuclear copper center consisting of two copper atoms, CuA and CuB, each coordinated by three histidines. The histidines are provided by two pairs of -helices forming a four -helix bundle motif (Figure 1). 7] Upon oxygen binding, a change of oxidation state is observed from Cu to Cu . 8] The type 3 copper-protein family includes not only tyrosinases and catecholoxidases but also hemocyanins, which are found extracellularly in the hemolymph of various mollusks and arthropods. Hemocyanins are responsible for the precise delivery of oxygen, in analogy to the hemoglobins. 9±11] Tyrosinases and hemocyanins have been investigated independently over the years, although comparative data have been reported. 10±15] The increasing volume of sequences and biophysical/biochemical data have suggested a study of both proteins, in a comparative way. Such comparative studies of type 3 copper protein sequences have revealed the existence of two different protein classes, which differ in their CuA and CuB environments. 11, 16, 17] CuA denotes the copper binding site closer to the N terminus, whereas CuB is the copper binding site closer to the C terminus. Figure 1. Structure of monoand binuclear copper centers. i) Binuclear copper centers (orange) bind dioxygen (red) in a TMside-on∫ coordination between two copper atoms as shown by a bioinorganic complex (ia) and the active site of the hemocyanin of the horseshoe crab Limulus polyphemus (ib). 30] ii) Crystallographic structure of a bioinorganic complex (iia), which is equivalent to a half active site of Limulus polyphemus hemocyanin (iib). It reveals that even a mono copper center can bind oxygen in a TMside-on∫ coordination. To date no protein has been described containing such a mononuclear active site.
Journal of Biological Chemistry | 1999
Elmar Jaenicke; Heinz Decker; Wolfgang Gebauer; Jürgen Markl; Thorsten Burmester
Hemocyanins are copper-containing, respiratory proteins that occur in the hemolymph of many arthropod species. Here we report for the first time the presence of hemocyanins in the diplopod Myriapoda, demonstrating that these proteins are more widespread among the Arthropoda than previously thought. The hemocyanin ofSpirostreptus sp. (Diplopoda: Spirostreptidae) is composed of two immunologically distinct subunits in the 75-kDa range that are most likely arranged in a 36-mer (6 × 6) native molecule. It has a high oxygen affinity (P 50 = 4.7 torr) but low cooperativity (h = 1.3 ± 0.2).Spirostreptus hemocyanin is structurally similar to the single known hemocyanin from the myriapod taxon, Scutigera coleoptrata (Chilopoda), indicating a rather conservative architecture of the myriapod hemocyanins. Western blotting demonstrates shared epitopes of Spirostreptus hemocyanin with both chelicerate and crustacean hemocyanins, confirming its identity as an arthropod hemocyanin.
FEBS Letters | 2008
Dorothea Nillius; Elmar Jaenicke; Heinz Decker
Phenoloxidases and hemocyanins have similar type 3 copper centers although they perform different functions. Hemocyanins are oxygen carriers, while phenoloxidases (tyrosinase/catecholoxidase) catalyze the initial step in melanin synthesis. Tyrosinases catalyze two subsequent reactions, whereas catecholoxidases catalyze only the second one. Recent results indicate that hemocyanins can also function as phenoloxidases and here we show for the first time that hemocyanin can be converted to phenoloxidase. Furthermore, its substrate specificity can be switched between catecholoxidase and tyrosinase activity depending on effectors such as hydroxymethyl‐aminomethan (Tris) and Mg2+‐ions. This demonstrates that substrate specificity is not caused by a chemical modification of the active site.
Developmental and Comparative Immunology | 2009
Elmar Jaenicke; Sebastian Fraune; Sandra May; Pinar Irmak; René Augustin; Christian Meesters; Heinz Decker; Martin Zimmer
In the Common woodlouse Porcellio scaber (Crustacea: Isopoda: Oniscidea), experimental immune challenge did not induce the expression of pro-phenoloxidase that, in most other invertebrates studied thus far, can be activated into phenoloxidase via an activation cascade upon immune challenge. Instead, Porcellio hemocyanin proved to exhibit catecholoxidase activity upon activation. However, none of the activating factors known from other invertebrates other than SDS-treatment resulted in activation of hemocyanin into a functional phenoloxidase in vitro. The distinct characteristics of isopod hemocyanin are reflected by the quaternary structure of the hemocyanin dodecamers that differs from that of other crustacean hemocyanins in that the two hexamers share a common 3-fold rotation axis and have an angular offset of 60 degrees against each other. Accordingly, the sequence of Porcellio hemocyanin can be distinguished clearly from other crustacean hemocyanins and in a phylogenetic analysis forms a cluster with other isopod and amphipod hemocyanins. We propose a peracarid-type hemocyanin that may have evolved in response to its required multiple functions in respiration and immune response, while phenoloxidase sensu strictu is lacking.
FEBS Journal | 2008
Elmar Jaenicke; Heinz Decker
Phenoloxidases occur in almost all organisms, being essentially involved in various processes such as the immune response, wound healing, pigmentation and sclerotization in arthropods. Many hemocyanins are also capable of phenoloxidase activity after activation. Notably, in chelicerates, a phenoloxidase has not been identified in the hemolymph, and thus hemocyanin is assumed to be the physiological phenoloxidase in these animals. Although phenoloxidase activity has been shown for hemocyanin from several chelicerate species, a characterization of the enzymatic properties is still lacking. In this article, the enzymatic properties of activated hemocyanin from the tarantula Eurypelma californicum are reported, which was activated by SDS at concentrations above the critical micellar concentration. The activated state of Eurypelma hemocyanin is stable for several hours. Dopamine is a preferred substrate of activated hemocyanin. For dopamine, a KM value of 1.45 ± 0.16 mm and strong substrate inhibition at high substrate concentrations were observed. Typical inhibitors of catecholoxidase, such as l‐mimosine, kojic acid, tyramine, phenylthiourea and azide, also inhibit the phenoloxidase activity of activated hemocyanin. This indicates that the activated hemocyanin behaves as a normal phenoloxidase.
FEBS Journal | 2005
Mariano Beltramini; Nadia Colangelo; Folco Giomi; Luigi Bubacco; Paolo Di Muro; Nadja Hellmann; Elmar Jaenicke; Heinz Decker
The hemocyanin of the tiger shrimp, Penaeus monodon, was investigated with respect to stability and oxygen binding. While hexamers occur as a major component, dodecamers and traces of higher aggregates are also found. Both the hexamers and dodecamers were found to be extremely stable against dissociation at high pH, independently of the presence of calcium ions, in contrast to the known crustacean hemocyanins. This could be caused by only a few additional noncovalent interactions between amino acids located at the subunit–subunit interfaces. Based on X‐ray structures and sequence alignments of related hemocyanins, the particular amino acids are identified. At all pH values, the p50 and Bohr coefficients of the hexamers are twice as high as those of dodecamers. While the oxygen binding of hexamers from crustaceans can normally be described by a simple two‐state model, an additional conformational state is needed to describe the oxygen‐binding behaviour of Penaeus monodon hemocyanin within the pH range of 7.0 to 8.5. The dodecamers bind oxygen according to the nested Monod–Whyman–Changeaux (MWC) model, as observed for the same aggregation states of other hemocyanins. The oxygen‐binding properties of both the hexameric and dodecameric hemocyanins guarantee an efficient supply of the animal with oxygen, with respect to the ratio between their concentrations. It seems that under normoxic conditions, hexamers play the major role. Under hypoxic conditions, the hexamers are expected not to be completely loaded with oxygen. Here, the dodecamers are supposed to be responsible for the oxygen supply.
Food Chemistry | 2015
Petra Fronk; Hermann Hartmann; Margarita Bauer; Even Solem; Elmar Jaenicke; Stefan Tenzer; Heinz Decker
Polyphenoloxidases (PPO) of the type-3 copper protein family are considered to be catecholoxidases catalyzing the oxidation of o-diphenols to their corresponding quinones. PPO from Grenache grapes has recently been reported to display only diphenolase activity. In contrast, we have characterized PPOs from Dornfelder and Riesling grapes which display both monophenolase and diphenolase activity. Ultracentrifugation and size exclusion chromatography indicated that both PPOs occur as monomers with Mr of about 38kDa. Non-reducing SDS-PAGE shows two bands of about 38kDa exhibiting strong activity. Remarkably, three bands up to 60kDa displayed only very weak PPO activity, supporting the hypothesis that the C-terminal domain covers the entrance to the active site. Molecular dynamic analysis indicated that the hydroxyl group of monophenolic substrates can bind to CuA after the flexible but sterically hindering Phe 259 swings away on a picosecond time scale.
Developmental and Comparative Immunology | 2010
Beatrice Mindykowski; Elmar Jaenicke; Stefan Tenzer; Sebahattin Cirak; Thorsten Schweikardt; Hansjoerg Schild; Heinz Decker
Allergens from cockroaches cause major asthma-related health problems worldwide. Among them Per a 3 belongs to the most potent allergens. Although the sequences of some members of the Per a 3-family are known, their biochemical and biophysical properties have not been investigated. Here we present for the first time a thorough structural characterization of these allergens, which have recently been tested to induce an increase of allergy specific indicators in blood of Europeans. We isolated two Per a 3 isoforms, which occur freely dissolved in the hemolymph as hexamers with molecular masses of 465+/-25kDa (P II) and 512+/-25kDa (P I). Their sedimentation coefficients (S(20,W)) were determined to be 17.4+/-0.7 S (P II) and 19.0+/-0.9 S (P I), respectively. Sequence analysis revealed that P II consists of two subunit types known as allergens Per a 3.01 and Per a 3.0201, while PI consists of a new allergenic subunit type designated as Per a 3.03. A 3D model of the hexameric allergen Per a 3 was obtained by homology modelling. Almost all of the recently predicted 11 putative antigenic peptides and reported IgE-epitopes could be located on the surface of the hexamer, thus being freely accessible in the hexameric structure of the native molecules. We propose this might contribute to their allergic potential as well as their extreme stability with respect to temperature.