In this issue


179 Using comparative genomics to uncover new kinds of protein-based metabolic organelles in bacteria

Julien Jorda, David Lopez, Nicole M. Wheatley, and ToddO.Yeates

In many bacteria, key metabolic reactions in the cell take place inside giant proteinaceous shells reminiscent of viral capsids. Diverse bacteria use these microcompartments (or MCPs) to carry out different reactions. A few of these have been studied experimentally, including the carboxysome and MCPs for metabolizing propanediol and ethanolamine, but other encapsulated reactions appear likely. In this paper, the database of sequenced bacterial genomes was analyzed systematically to infer the existence of additional encapsulated pathways by genomic context methods. Of particular interest is a presumptive ‘Grp’ microcompartment, wherein the key encapsulated reaction is based on a glycyl radical mechanism. 1

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153 Linkers in the structural biology of protein-protein interactions

Vishnu Priyanka Reddy Chichili, Veerendra Kumar, and J.Sivaraman

Protein-protein interactions are involved in various catalytic and biological processes. To date, there are numerous protein-protein interactions that cannot be determined because of the transient nature of binding. Here, the authors analyze the usage of linkers to trap protein-protein/peptide interactions for structural studies. Glycine-rich linkers have been proven useful to retain unstable interactions by creating a covalent link between the proteins to form a stable protein-protein complex. The lengths of linkers vary from 2 to 31 amino acids, optimized for each condition so that the linker does not impose any constraints on the interactions of the linked partners. 2

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231 Chimeragenesis of distantly-related proteins by noncontiguous recombination

Matthew A. Smith, Philip A. Romero, Timothy Wu, Eric M. Brustad, and Frances H. Arnold

The authors present a computational approach to identifying structural elements that can be swapped among homologous proteins. They design a functional beta-glucosidase that derives approximately half of its sequence from each of two parent enzymes from different kingdoms of life. The crystal structure of this chimera shows that each ‘block’ conserves the structure from its corresponding parent. This simple protein recombination method can be used to design chimeras of distantly-related parents for protein structure elucidation and directed evolution. 3

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139 Halogen bonding (X-bonding): A biological perspective

Matthew R. Scholfield, Crystal M. Vander Zanden, Megan Carter, and P. Shing Ho

Halogens are found in a large number of small molecules and secondary metabolites that serve as potent inhibitors against therapeutic targets. This review provides an overview of halogen bonding (or X-bonding), which, like the better-known hydrogen bond, is primarily an electrostatic molecular interaction. X-bonds have been shown to contribute upwards of 1,000-fold increase in the specificity of a halogenated ligand towards its protein target and, therefore, have the potential to serve as an important atomic tool in the design strategy for new therapeutic inhibitors. 4

Illustration 4.

Ancillary

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