Ephrins

In this section we will provide only a brief summary of multicopper blue oxidases and some of the novel members of these family that we identified because of their unique sequence characteristics. For more detailed information we direct the readers to excellent reviews and a book that were published in the past few years (Solomon et al., 1996 Messerschmidt, 1997). 

Multicopper blue oxidases are synthesized as a single polypeptide chain, which is composed of three BCB domains in the case of laccases (LC) and ascorbate oxidases (AO) and six such domains in ceruloplasmin (CP) and hephaestin (HP). Structurally they are arranged in a triangular manner. These enzymes, along with heme-copper oxidases (cytochrome c oxidases and quinol-oxidases) and a cyanide-resistant alternative oxidase found in mitochondria of plants and fungi, are the only known enzymes capable of catalyzing four-electron reduction of dioxygen to water. In the 

The type 1 copper site, which is the substrate oxidation site, is maintained in the C-terminal BCB domain (domain 3 in AO and LC and 

Laccases are found in bacteria, ffingi, plants, and insects. They catalyze oxidation of a variety of phenolic and inorganic substances with values 

Laccases are usually monomers and are considered to be the simplest blue copper oxidases. A fungal genome may express multiple LC isoforms that differ by their substrate specihcity, pH optimum, and redox potentials (Germann et al., 1988 Wahleithner et al., 1996 Xu, 1996 Yaver and 

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VEGFs, the angiopoietins, the Ephrins and Notch molecules stand out as they act specifically or preferentially on the vascular system and have, thus, to be considered as key regulatory molecules of the angiogenic cascade [3]. 

Inhibitors of the Angiopoietin/Tie-2 and Ephrin/Eph systems are in preclinical development which parallels the biological target validation of these molecules. As vascular assembly, maturation, and homeostasis regulating molecules, therapeutic interference with these molecular systems may hold promise for a number of vascular indications. 

Ephrins are a group of membranous ligands, which function through a family of receptor tyrosine kinases (Ephs). Ephrin/Eph-mediated signaling processes are involved in morphogenetic processes taking place e.g. during the development of the nervous system or the vasculature. 

Ephrin receptor B2 (EphB2) Inactive insert, and C-terminal tail Juxtamembrane and N-terminal lobe inhibited by... 

Myshkin, E. and Wang, B. Chemometrical classification of ephrin ligands and eph kinases using GRID/CPCAapproach./. Chem. Inf. Comput. Sci. 2003, 43, 1004-1010. 

Dolichotheline (111) is a histamine-derived alkaloid produced by the cactus Dolichothele sphaerica Britton and Rose (Cactaceae) native to southern Texas and northern Mexico. The alkaloid was first isolated in 1969 by Rosenberg and Paul (160). Spectroscopic data suggested structure 111, 4(5)-(iV-isovalerylaminoethyl)imidazole or 7V -isovalerylhistamine. The structure was proved by synthesis. Refluxing of histamine with isovaleric anhydride yielded 111, identical to the natural product (160). In addition to the major alkaloid dolichotheline, five minor alkaloids have been isolated (161). These were identified as A-methylphenethylamine, /i-O-methylsyn-ephrine, vV-methyltyramine, synephrine, and / -0-ethylsynephrine by IR, NMR, and comparison to authentic materials / -0-ethylsynephrine was probably an artifact of synephrine, since it was not found in a second extraction attempt when no ethanol was used. 

A. Expression Profiles and Biological Roles of Ephs and Ephrins. 67... 

Analysis of Eph and ephrin protein expression has been carried out in several species including zebrafish, Xenopus, mouse, rat, and chicken embryos (reviewed in Boyd and Lackmann, 2001). They are broadly... 

Fig. 1. Schematic representation of the domain organization of Eph receptors and ephrins. SAM, sterile alpha motif.

Fig. 2. Structures of the extracellular domains of Ephs and ephrins. The molecular surfaces (semi-transparent) are also indicated. (A) Structure of the ligand-binding domain of EphB2. The N- and C-termini of the molecule are labeled, as are the class-specificity loop (H-I) and the ligand-binding loops that are largely disordered in the absence of bound ephrin. (B) Structure of the extracellular receptor-binding domain of ephrin-B2. Indicated is the location of the receptor-binding G-H loop. (C) Structure of the EphB2/ephrin-B2 tetramer. Eph receptors are blue and ephrins are green. The high-affinity dimerization interfaces are indicated by arrows. (See Color Insert.)...

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