Current Drug Targets - Volume 5, Issue 2, 2004

The value of structure analysis of proteins in rational drug design is undisputed. The ability to visualize the three dimensional structure of a receptor or enzyme provides a unique view of the residues that make up the protein's ligand binding or catalytic site. The analysis of complexes with ligands or inhibitors provides many clues on the roles that these residues play in the functioning of the molecule. The information derived from t Read More

Despite the fact that influenza is a disease which affects millions of people, sometimes with fatal consequences, there has not, until recently, been any drug effective against all strains. Vaccines may be relatively or totally ineffective, so drugs are needed. Random screening of many thousands of compounds by pharmaceutical companies has resulted in only two compounds, amantadine and rimantidine, which target the M2 ion Read More

Malaria remains a major disease of mankind, and resistance to existing therapeutics is rapidly emerging. Limited financial investment to develop new therapeutics requires the careful selection of well-defined targets from the causative parasite, Plasmodium falciparum. In these circumstances, protein crystallography can provide valuable structural detail to facilitate both the selection of suitable targets and the d Read More

Amyloid fibres are stable, persistent and highly ordered aggregates of mis-folded protein that accumulate in tissues and are a prominent feature of the pathology of a wide range of human diseases. The presumed role of amyloid as a causative factor of tissue damage is based largely on 'guilt by association'. However, growing understanding of the nature of amyloid, its formation by a nucleated growth mechanism from destabilis Read More

Immunoglobulin light chain (LC) proteins exhibit the greatest sequence variability of all proteins associated with amyloid disease. The hallmark event in amyloidogenesis is a change in the secondary and / /or tertiary structure of a normal, soluble protein, that fosters selfaggregation and fibril formation. The structural heterogeneity of light chain proteins has hampered understanding of the precise mechanisms involved in fibril Read More

The number of protein crystal structures being refined to atomic resolution is increasing each year as well as the size of proteins being studied. There are currently 346 structures in the protein data bank which have been refined to or beyond atomic resolution. The benefits of atomic resolution X-ray data are discussed along with a number of structural examples of biomedically relevant proteins. The complementary r Read More

Cancer is a growing problem for human health world-wide. Dramatic breakthroughs have increased our understanding of the molecular mechanisms involved in the process of tumorigenesis, allowing us to develop more refined anti-cancer treatments, expanding the repertoire of available anti-cancer drugs, and increasing the efficiency of their delivery to malignant cells. Nevertheless, even with improved understa Read More

DNA polymerase is one of the most important target molecules of antitumor agents, especially for antimetabolite nucleosides that include 1-β-D-arabinofuranosylcytosine (araC) and 2'-deoxy-2',2'-difluorocytidine (gemcitabine). There are several subtypes of mammalian DNA polymerases and their localization and function have been clarified. DNA polymerase α, δ and ε have been implicated to be responsible for DNA replicatio Read More

Parkinson's disease (PD) is a serious motor disorder and it is the second most common brain degenerative disease in human. PD is known to be caused by degeneration of dopamine neurons in the substantia nigra but the cause of cell death is largely unknown. Mammalian neurokinins [NKs] are a group of neuropeptides that include substance P (SP; neurokinin-1, NK-1), substance K (SK; NK-2; neurokinin A), and neuromedin K Read More