CC+: a relational database of coiled-coil structures

We introduce the CC+ Database, a detailed, searchable repository of coiled-coil assignments, which is freely available at http://coiledcoils.chm.bris.ac.uk/ccplus. Coiled coils were identified using the program SOCKET, which locates coiled coils based on knobs-into-holes packing of side chains between α-helices. A method for determining the overall sequence identity of coiled-coil sequences was introduced to reduce statistical bias inherent in coiled-coil data sets. There are two points of entry into the CC+ Database: the ‘Periodic Table of Coiled-coil Structures’, which presents a graphical path through coiled-coil space based on manually validated data, and the ‘Dynamic Interface’, which allows queries of the database at different levels of complexity and detail. The latter entry level, which is the focus of this article, enables the efficient and rapid compilation of subsets of coiled-coil structures. These can be created and interrogated with increasingly sophisticated pull-down, keyword and sequence-based searches to return detailed structural and sequence information. Also provided are means for outputting the retrieved coiled-coil data in various formats, including PyMOL and RasMol scripts, and Position-Specific Scoring Matrices (or amino-acid profiles), which may be used, for example, in protein-structure prediction

Maintaining and breaking symmetry in homomeric coiled-coil assemblies

Higher order coiled coils with five or more helices can form α-helical barrels. Here the authors show that placing β-branched aliphatic residues along the lumen yields stable and open α-helical barrels, which is of interest for the rational design of functional proteins; whereas, the absence of β-branched side chains leads to unusual low-symmetry α-helical bundles

A Novel Tetrameric PilZ Domain Structure from Xanthomonads

PilZ domain is one of the key receptors for the newly discovered secondary messenger molecule cyclic di-GMP (c-di-GMP). To date, several monomeric PilZ domain proteins have been identified. Some exhibit strong c-di-GMP binding activity, while others have barely detectable c-di-GMP binding activity and require an accessory protein such as FimX to indirectly respond to the c-di-GMP signal. We now report a novel tetrameric PilZ domain structure of XCC6012 from the plant pathogen Xanthomonas campestris pv. campestris (Xcc). It is one of the four PilZ domain proteins essential for Xcc pathogenicity. Although the monomer adopts a structure similar to those of the PilZ domains with very weak c-di-GMP binding activity, it is nevertheless interrupted in the middle by two extra long helices. Four XCC6012 proteins are thus self-assembled into a tetramer via the extra heptad repeat α3 helices to form a parallel four-stranded coiled-coil, which is further enclosed by two sets of inclined α2 and α4 helices. We further generated a series of XCC6012 variants and measured the unfolding temperatures and oligomeric states in order to investigate the nature of this novel tetramer. Discovery of this new PilZ domain architecture increases the complexity of c-di-GMP-mediated regulation

Selective deprotection of N-Boc-imidazoles and pyrazoles by NaBH4 in EtOH

Herein, a novel method for the selective N-Boc deprotection of imidazoles, benzimidazoles and pyrazoles in good to excellent yield (75-98%), using NaBH4 in EtOH at room temperature is reported. Under these conditions, the primary Boc-protected amines and a number of N-Boc-protected aromatic heterocycles such as pyrrole and indole remain completely intact. © AUTHOR (S)

Peptide and protein building blocks for synthetic biology: From programming biomolecules to self-organized biomolecular systems

There are several approaches to creating synthetic-biological systems. Here, we describe a molecular-design approach. First, we lay out a possible synthetic-biology space, which we define with a plot of complexity of components versus divergence from nature. In this scheme, there are basic units, which range from natural amino acids to totally synthetic small molecules. These are linked together to form programmable tectons, for example, amphipathic alpha-helices. In turn, tectons can interact to give self-assembled units, which can combine and organize further to produce functional assemblies and systems. To illustrate one path through this vast landscape, we focus on protein engineering and design. We describe how, for certain protein-folding motifs, polypeptide chains can be instructed to fold. These folds can be combined to give structured complexes, and function can be incorporated through computational design. Finally, we describe how protein-based systems may be encapsulated to control and investigate their functions

Autotaxin inhibitors: A patent review

Introduction: Autotaxin (ATX) is a lysophospholipase D enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline. LPA is a bioactive lipid mediator that activates several transduction pathways, and is involved in migration, proliferation and survival of various cells. Thus, ATX is an attractive medicinal target. Areas covered: The aim of this review is to summarize ATX inhibitors, reported in patents from 2006 up to now, describing their discovery and biological evaluation. Expert opinion: ATX has been implicated in various pathological conditions, such as cancer, chronic inflammation, neuropathic pain, fibrotic diseases, etc. Although there is an intensive effort on the discovery of potent and selective ATX inhibitors in order to identify novel medicinal agents, up to now, no ATX inhibitor has reached clinical trials. However, the use of ATX inhibitors seems an attractive strategy for the development of novel medicinal agents, for example anticancer therapeutics. © 2013 Informa UK, Ltd

Reduction of pentafluorophenyl esters to the corresponding primary alcohols using sodium borohydride

Primary alcohols and chiral N-protected 2-amino alcohols can be obtained in high yields from the reaction of pentafluorophenyl esters of the corresponding carboxylic acids with sodium borohydride in THF under mild conditions. This reductive method is rapid and compatible with various functional groups as well as with the most common N-protective groups Z, Boc and Fmoc. © 2007 Elsevier Ltd. All rights reserved