Spring-loading the active site of cytochrome P450

Enzymes differ from other catalysts in the exceptional substrate selectivity they exhibit.  However, the active sites of related enzymes are often very similar, even though different substrates are acted upon (for example in the superfamily of cytochrome P450s).  How does a given enzyme preferentially bind a particular substrate?  In a new paper appearing in the jounal Metallomics, Chemistry grad student Marina Dang and Profs. Susan Sondej Pochapsky and Thomas Pochapsky use nuclear magnetic resonance (NMR) to identify a helical structure remote from the active site of the enzyme cytochrome P450cam that is responsive to changes in substrate.  They propose that this helix can adjust the position of residues that contact substrate in the enzyme active site, much like the spring that holds batteries in place against electrical contacts in a flashlight.

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2010 Beckman Scholar Philip Braunstein ’12 discusses his research project in the Hedstrom lab at the last class meeting of Organic Chemistry CHEM 25a. Training the scholars in communicating science and improving the visibility of undergraduate research are key components of the Beckman Scholars program.

Photographs by Nathaniel Freedman

Can a “chemical rope” help treat ALS?

In this week’s issue of PNAS, Brandeis postdoc Jared Auclair and Chemistry grad student Kristin Boggio, together with Professors Greg Petsko, Dagmar Ringe, and Jeffrey Agar discuss Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis. Working from the hypothesis that the mechanism of the toxicity involves dimer destabilization and dissociation as an early step in SOD1 aggregation, they looked for mechanisms to stabilize SOD1 using chemical cross-linking. Cross-linking the dimer using 2 adjacent cysteine residues results in substantial stabilization of relevant SOD1 mutants.

A "Chemical rope" stabilizes SOD1 protein. Mutations that destabilize SOD1 in motor neurons are associated with familial ALS

Read more about Prof. Agar, this research, and its potential for this technique in the treatment of ALS at Brandeis NOW

New undergraduate specialization in Chemical Biology

The Brandeis Department of Chemistry now offers a B.A. or B.S. degree with specialization in Chemical Biology. The requirements for the degree are described in the university bulletin. — look in the section Requirements for the Major, towards the bottom.

More information: What Is Chemical Biology?

Nanomaterials in cells

From Bing Xu, one of the new faculty members in the Chemistry Department here at Brandeis, comes a new review on Applications of nanomaterials inside cells. Quantum dots, magnetic nanoparticles, nanowires, the works.

AAT

Prof. Anne Gershenson from Chemistry has been awarded a grant from the Alpha-1 Foundation to study protein structure related chain formation of Alpha-1 Antitrypsin.

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