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Research has been conducted on the hormone receptor-mimetic peptide mastoparan. The role of the GTP-binding protein Cdc42 in the mastoparan stimulus-secretion pathway has been investigated and the results suggest the involvement of this protein in the mastoparan-stimulated GTP-dependent pathway of insulin release.

Research has been conducted on the carboxypeptidase E, a sorting receptor directing the prohormone to the regulated sectretory pathway. The study of the structure and orientation of the membrane-binding domain at the C-terminus of the carboxypeptidase E and the results are reported.

Protein-DNA interactions and DNA distortions are analyzed from the crystal structure of RevErb-DNA complex. Data indicate marked and consistent DNA distortion occurs at a thymine-adenine step preceding the consensus hexameric recognition sequence of the DNA targets.

Research has been conducted on the amino-terminal ectodomain of the human thyrotropin receptor. The expression of this receptor at the CHO cells as a glycosylphosphatidylinositol-anchored molecule has been carried out and the results are presented.

Research has been conducted on the human melanin-concentrating hormone, an agonist at the human melanin-concentrating hormone receptors 1 and 2. The structural features of this neuropeptide necessary for the binding and activation of the receptors have been determined via the synthesis of the open-chain, Ala-substituted and truncated analogues and tested in the CHO cell binding assays.

Research describes the structure of the extracelular loop of human cholecystokinin-A receptor and its molecular contact with the C-terminal octapeptide of cholecystokinin. Results demonstrate unique molecular interactions involved in the binding process of the receptor and the octapeptide.

Research reveals that combined mutations in both single chain interleukin-5 and one-domain GM1 form backgrounds, involving glutamate 110 replacements along with other mutations, lead to partial antagonist interleukin-5 muteins. Data indicate that the receptor binding and activation epitopes are separate in interleukin-5.

The receptor-binding conformation of bombyxin has been found to be induced by alanine(B15). Alanine(B15) is located in a prominent position at the rim of a putative binding pocket. It has been shown to be necessary in that position.

The N-terminal fragment of human parathyroid hormone receptor 1 (PRHR1) has been found to be a hormone-binding domain and to have a distinct disulfide pattern. In order to study it, the truncated receptor was expressed in the cytosol of Escherichia coli as inclusion bodies. Oxidative refolding of the inclusion body material brought on soluble stable monomeric protein. Overexpression of the N-terminal ligand-binding domain of class B G-0rtoein-coupled receptors and subsequent refolding to a functional protein domain is feasible as a means to getting large amounts of protein for structural and ligand-binding studies.

Findings of a study show loss of estrogen receptor (ER) DNA-binding function in extracts from some primary breast tumors and in ER or ER-DNA-binding domain (DBD) exposed to thiol-reacting oxidants results from an asymmetric zinc finger susceptibility to disulfide formation that prevents dimerization. ER-DBD has several strategically located methionine resides, but they are less susceptible to oxidation than the thiol groups, and offer no protection against cysteine oxidation and so consequent loss of ER DNA-binding function.

Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 of these novel receptor systems have been identified and the emphasis has shifted to searching for novel signalling molecules. Thus, multiple neurotransmitter systems have eluded pharmacological detection by conventional means and the tremendous physiological implications and potential for these novel systems as targets for drug discovery remains unexploited. The discovery of all the GPCR genes in the genome and the identification of the unsolved receptor-transmitter systems, by determining the endogenous ligands, represents one of the most important tasks in modern pharmacology.

The interaction of peroxisome proliferator-activated receptor (PPAR) alpha with ligands has been studied using a fluorescence-based method. PPARs are nuclear hormone receptors that play important roles in lipid metabolism. A synthetic fluorescent long-chain fatty acid, parinaric acid is used as the probe. Results show the long-chain fatty acid binds with PPAR alpha with high affinity and can be used in monitoring protein-ligand interactions by the receptor.

While regulation of receptor function is known to occur at many levels (e.g. transcriptional, post-translational), it is generally perceived that a tissue either expresses or does not express a particular receptor in an all-ornone fashion. Many pathological (e.g. tissue injury) and physiological (e.g. angiogenesis) processes have, however, been shown to be associated with the transcriptional induction of specific receptors. Induced receptors are not confined to any particular class, but range from G protein-coupled receptors to receptor tyrosine kinases. The potential implications of de novo receptor expression are profound with respect to potential novel therapeutic targets in specific disease states. Further, this observation may explain unexpected side-effects in the pharmacotherapy of existing disease states. In this article Lucy Donaldson, Michael Hanley and Amparo Villablanca discuss circumstances under which de novo receptor induction has been described, potential mechanisms of induction and the implications for pharmacology.

A novel kinetic analysis model was used to study insulin receptor autophosphorylation. The fast reaction phase, slow reaction phase and a partition function for both phases are studied in the kinetic model of autophosphorylation. Insulin was found to enhance autophosphorylation through a 10-fold increase in the rate constant for the fast reaction phase and a two-fold increase in the rate constant of the partition function favoring the fast reaction phase. The juxtamembrane sites of the insulin receptor was found to react primarily during the slow reaction phase. The carboxy-terminal and central autophosphorylation domains react in the fast reaction phase.

On his canvas entitled 'La trahison des Images' ('The Perfidy of Images'), Rene Magritte painted a tobacco pipe in a very realistic manner and added the words: 'Ceci n'est pas une pipe' ('This is not a pipe'). In similar style, it is of prime importance to state that the first three-dimensional (3D) models of G protein-coupled receptors (GPCRs) that have been defined and displayed are definitely not GPCRs and never will be. However, they probably represent a very important breakthrough in our understanding of GPCR structure and function as well as being a source of novel working hypotheses that can be experimentally explored. Several generations of scientists have elaborated their research on the concept of hormone-receptor interaction without having access to any structural representation of this molecular complex. Thus, for many years receptors remained only indirectly characterized through their functions or their binding properties. As a consequence, a number of important issues are still to be addressed. How does a hormone bind and activate its receptor? How does an antagonist inactivate a receptor? What is a partial agonist? What are the molecular mechanisms of signal transduction and modulation? Obviously, answers to these questions are of prime importance for medicinal chemists in their attempts to rationalize drug design.

A study was done on the composition of the androgen receptor protein complex during the process of hormone-induced receptor transformation in intact cells. Specific monoclonal antibodies were able to identify hsp90, hsp70 and hsp56. In addition, it was shown that the receptor complex undergoes large rearrangements prior to tight nuclear binding leading to the loss of different heat shock proteins. These findings suggest the presence of an antigenic epitope in the DNA-binding domain of the androgen receptor.

Research has been conducted on nuclear thyroid hormone receptor TR(beta)1.The authors report the identification of the thyroid hormone receptor's serine phosphorylation site in receptor's DNA-binding domain, and the identifications of mitogen-activated protein kinase docking site on thyroid hormone receptor induced by L-thyroxine.

Mutation of serine 431 to alanine in the third transmembrane alpha-helix of the luteinizing hormone/human chorionic gonadotropin receptor reduces cAMP production in response to human chorionic gonadotropin, indicating that serine 431 is involved in the stabilization of the active state of the receptor.