Owing to their detoxifying functions, and roles in drug metabolism as well as the prevention of atherosclerosis, mammalian or serum paraoxonases (PONs) are an intriguing subject of research and a prime therapeutic and engineering target. Initially identified in mammals, PON and PON-related genes have now been found in fowls, zebra fish, and even in invertebrates such as C. elegans. The more closely-related PON genes are divided into three classes or sub-families: PON1, PON2 and PON3, that share 60-70% sequence identity (Draganov and La Du, 2003). PONs are calcium-dependent hydrolases that catalyze the hydrolysis of a broad range of esters and ... Read more

The tumor suppressor protein p53 is crucial in preventing cancer as well as for achieving the therapeutic effects of both radiotherapy and much of chemotherapy. p53 responds to oncogene activation, DNA damage, hypoxia and other stresses by activating the expression of factors that trigger cell cycle arrest or programmed cell death (Vogelstein et al., 2000). Strong evidence that inactivation of p53 is required for cancer cell survival comes from accumulated data that p53 is inactivated by mutations in some 50% of all human tumors, regardless of patient age or tumor type. This makes p53 the most frequently mutated gene in ... Read more

Proteins show remarkable plasticity in their sequence composition and arrangement while preserving biological functions. This is made possible by the large number of amino acid units, often in the hundreds or thousands, that comprise the protein. The ability to change each and every amino acid in a protein drug has already contributed to significant clinical benefits: greater efficacy and less adverse effects by decreasing immunogenicity and functionally improved specificity. The native protein is optimized for its normal biological function. Scientists take the hint from nature and make it a therapeutic: a powerful force to perturb and correct a disease state.

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Protein modification and remodeling play an important role in basic biological studies, drug designs, vaccine developments, etc. Computer-assisted protein modification has been applied to predict the possible consequences, screen large number of candidates, and interpret the observations.

Granulocyte colony-stimulating factor (G-CSF) binds to its receptor on the surface of bone marrow-precursor cells and stimulates the production of neutrophils. In order to increase the half-life of G-CSF, an MIT group designed a number of G-CSF mutants in an effort to reduce its binding affinity to its receptor so that it can be released easily in endosomal compartments and recycled to the cell ... Read more