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An Introduction to Allosteric Regulation

21 August, 2007 - 2 min read

A fundamental process of life is the selective and efficient catalysis of chemical reactions by enzymes. Enzymes are usually proteins (ribozymes are one exception), and when these catalysts are chained together they form pathways. Enzyme pathways can be loosely described by their inputs and outputs. An even better abstraction than pathways though is to think in terms of networks. Networks have hubs which are critical to the operation of the network. [Vidal Lab is doing great work in this area of cancer proteomics]

In biology, allosteric enzymes are typically the regulatory elements in a catalytic network. More importantly, interactions distant from the catalytic site can induce changes in activity. One of the first examples of regulated enzyme networks is a system of 5 enzymes in bacteria which catalyze the conversion of L-Threonine to L-Isoleucine. Threonine dehydratase, the first enzyme in the pathway, is specifically inhibited by the end product of the pathway. This is simple feedback-inhibition, where buildup of the end product regulates and slows down the entire pathway by modulating the first step. This simple model illustrates an important aspect of protein interaction. It’s not good enough to simply say that enzyme A “interacts with” enzyme B. We need models that can express things like feedback, messaging, and other more abstracted language about protein relationships.

Compared to genomics, the proteomics universe appears to be pretty messy. Proteins interact in networks with enormous complexity. The challenges for a reverse engineering approach are overwhelming. There is no high-throughput method for reliably characterizing protein functions. Systems Biology is applying simplistic network models, and the Gene Ontology Consortium is working to develop a language for cellular functions. Both of these efforts have much to gain from structural biology.

Further Reading:

Ligand binding and allostery can emerge simultaneously

Is allostery an intrinsic property of all dynamic proteins?

The changing landscape of protein allostery