We demonstrate that incorporation of MnSalen into a protein scaffold enhances the chemoselectivity in sulfoxidation of thioanisole and find that both the polarity and hydrogen bonding of the protein scaffold play an important role in tuning the chemoselectivity.

The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl) methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A has been determined at 2.25-A resolution by x-ray crystallographic methods. This is the first example of a sulfodiimine-containing inhibitor binding to a zinc enzyme, and the structure of the enzyme-inhibitor complex reveals that the tetrahedral sul...

A key question in the biological activation of oxygen is how the protein matrix regulates the delivery of oxygen to its site of activation. We are using Escherichia coli copper amine oxidase as a model system to investigate the roles played by both local active site residues as well as long range interactions in this process. We have generated active site mutants, as well as mutants in the puta...

One of the greatest challenges in biotechnology and in biochemistry is the ability to design efficient enzymes. In fact, such an ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. Despite some progress on this front, most of the advances have been made by placing the reacting fragments in the proper places rather than by optimiz...

Influenza is a yearly seasonal threat and major cause of mortality, particularly in children and the elderly. Although neuraminidase inhibitors and M2 protein blockers are used for medication, drug resistance has gradually emerged. Thus, the development of effective anti-influenza drugs targeting different constituent proteins of the virus is urgently desired. In this light, we carried out mole...

Arginase is a metalloenzyme which hydrolyzes L-arginine to L-ornithine and urea. Since its discovery, in the early 1900s, this enzyme has gained increasing attention, as literature reports have progressively pointed to its critical participation in regulating nitric oxide bioavailability. Indeed, accumulating evidence in the following years would picture arginase as a key player in vascular hea...

The ability to redesign enzymes to catalyze noncognate chemical transformations would have wide-ranging applications. We developed a computational method for repurposing the reactivity of metalloenzyme active site functional groups to catalyze new reactions. Using this method, we engineered a zinc-containing mouse adenosine deaminase to catalyze the hydrolysis of a model organophosphate with a ...

Numerous microorganisms oxidize sulfur for energy conservation and contribute to the global biogeochemical sulfur cycle. We have determined the 1.7 angstrom-resolution structure of the sulfur oxygenase reductase from the thermoacidophilic archaeon Acidianus ambivalens, which catalyzes an oxygen-dependent disproportionation of elemental sulfur. Twenty-four monomers form a large hollow sphere enc...