Featured System - August 2009
Short description: Centuries ago, both the ancient Greeks and native Americans discovered that willow bark and other plants can dull pain.
Centuries ago, both the ancient Greeks and native Americans discovered that willow bark and other plants can dull pain. By analyzing these traditional cures, scientists in the nineteenth century extracted the active molecule, salicylic acid, and developed a modified molecule with better drug properties, acetylsalicylic acid or aspirin. In our bodies, aspirin blocks an enzyme that builds one of the molecules of pain signaling. Plants, on the other hand, use salicylic acid for an entirely different type of signaling.
Plants have developed a complex and multi-layered system to protect themselves from attack by bacteria and viruses. When a leaf gets infected, for instance by tobacco mosaic virus, the local cells make the ultimate sacrifice, inducing a form of programmed cell death. This helps control the spread of the virus by proactively removing all infectable cells in the neighborhood. At the same time, the plant launches a more systemic defense. It sends a signal to all of its distant parts, telling them to build defensive proteins and ready themselves for attack. These defenses are costly, and may result in stunted growth, but this is better than completely losing the battle against the attacker.
Methyl salicylate, the methyl ester of salicylic acid, is one of the signals that spreads through plants, readying them for attack. Methyl salicylate is a familiar molecule, since it provides the distinctive taste and smell of wintergreen flavorings. It is used as a neutral messenger, which is created by cells under attack and delivered to cells throughout the plant. Then, the enzyme SABP2 (salicylic acid binding protein 2) takes methyl salicylate and cleaves off the methyl group, releasing active salicylic acid, which then stimulates the production of defensive proteins in the target cells.
SABP2 was originally discovered based on its ability to bind to salicylic acid (hence its name), but the recent structure of the protein solved by researchers at the NESG revealed its role in cleavage of methyl salicylate and inhibition of the reaction by the product, salicylic acid. The structure, available in PDB entry 1y7i, shows that SABP2 is one of a class of alpha/beta hydrolase enzymes that cleave small esters and other molecules. The active site completely surrounds the molecule, recognizing both the distinctive aromatic ring and the acidic group. A catalytic triad reminiscent of the digestive serine proteases performs the cleavage reaction. Based on this structure, researchers have designed analogues of salicylic acid to probe signaling methods in other plants. To explore this structure in more detail, you can click on the image below for an interactive Jmol view of the active site.
The JSmol tab below displays an interactive JSmol.
Vav1 (in blue and green) interacts with two key switch loops in Rac1 (the switch loops are colored bright red in this representation). The typical interaction between guanine nucleotide exchange factors and GTPases involves other regions of the GTPase, but since the Vav1 structure is stabilized by the small cysteine-rich domain (colored green here, with two zinc ions in magenta), it can focus its attention on the switch loops. This makes Vav1 more promiscuous than other guanine exchange factors.
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