Current Pharmaceutical Design - Volume 15, Issue 31, 2009

Zinc (Zn) metal ion along with other transition metals like copper and iron are of vital significance in living organisms with zinc being the second most abundant transition metal ion in living organism following iron. Zn(II) exhibits remarkable stability in redox processes due to its d10 electronic configuration and is known to be indispensable to growth and development, to metabolic pathways as well as to transmission of the gen Read More

Matrix metalloproteinases are involved in many biological processes and in a large set of diseases. In the last twenty years the genetics, functions, and the structural features of this family of proteolytic enzymes have been investigated and a large number of synthetic inhibitors designed and tested. A better knowledge of the dynamical features of these proteins can be relevant not only to reveal new biological activities but als Read More

The fusion of therapeutics and diagnostic medicine in an effort to provide individualized pharmacotherapy frequently requires the manipulation of drugs that target different enzymes and receptors. To this end, and as a strategy to increase the efficiency of drug development pipelines, new chemical entities are often developed that interact with more than one target. Angiotensin-converting enzyme (ACE), its homologue ACE Read More

In recent decades, the most successful strategy for controlling blood pressure has been inhibition of the angiotensin-converting enzyme (ACE). ACE inhibitors of chemical synthesis (captopril, enalapril, ramipril and trandolapril) have been widely used clinically to reduce mortality in patients with heart failure, and in patients with recent myocardial infarction and heart failure or marked left ventricular dysfunction. In addition to pre Read More

Insulin-degrading enzyme (IDE) or insulysin is a highly conserved Zn2+ -dependent endopeptidase with an “inverted” HxxEH motif. In vivo, IDE contributes to regulate the steady state levels of peripheral insulin and cerebral amyloid β peptide (Aβ) of Alzheimer's disease. In vitro, substrates of IDE include a broad spectrum of peptides with relevant physiological functions such as atrial natriuretic factor, insulin-like growth fact Read More

During the last few years a novel role for previously known Zn(II) aminopeptidases has emerged, attracting a great deal of scientific interest to these molecules. Aminopeptidases appear now to play a key role in the last, yet crucial, proteolytic steps that generate small peptides for presentation onto MHC class I molecules so that the mature MHCpeptide complexes can be recognized by cytotoxic T-lymphocytes. In th Read More

Botulinum toxin has long been known for its paralytic effects on the human voluntary musculature via inhibition of acetylcholine release at neuromuscular junctions. Its original clinical use for the treatment of strabismus has expanded significantly to include neurological conditions related to muscle hyperactivity and/or spasticity (e.g., dystonia, spasticity, tics, tremor, dysphonia). Recently, botulinum toxin has been s Read More

LIM (Lin-11, Isl-1, Mec-3), RING (Really interesting new gene), PHD (Plant homology domain) and MYND (myeloid, Nervy, DEAF-1) domains are all zinc-binding domains that ligate two zinc ions. Unlike the better known classical zinc fingers, these domains do not bind DNA, but instead mediate interactions with other proteins. LIM-domain containing proteins have diverse functions as regulators of gene expression, cell adhesion a Read More

The ubiquitin proteasome system (UPS) plays a fundamental role in maintaining the correct balance of protein levels inside all living cells. Degradation of proteins by this pathway is essential for most cellular processes including cell signalling, DNA repair, apoptosis and gene transcription. Any disruption to the system is likely to have severe consequences which may lead to disorders including neurodegenerati Read More

The RING (Really Interesting New Gene) family is the largest type of E3 ubiquitin ligases. RING finger domains bind two zinc ions in a unique “cross-brace” arrangement through a defined motif of cysteine and histidine residues. This arrangement endows the RING domain with a globular conformation, characterized by a central α-helix and variable-length loops separated by several small β-strands. RING E3 ubiquitin ligase Read More