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Knowledge of structural relationships in proteins is increasingly proving very useful for in silico characterizations and is also being exploited as a prelude to almost every investigation in functional and structural genomics. A thorough understanding of the crucial features of a fold becomes necessary to realize the full potential of such relationships. To illustrate this, structures containing the legume lectin-like fold were chosen for a detailed analysis since they exhibit a total lack of sequence similarity among themselves and also belong to diverse functional families. A comparative analysis of 15 different families containing this fold was therefore carried out, which led to the determination of the minimal structural principles or the determining region of the fold. A critical evaluation of the structural features, such as the curvature of the front sheet, the presence of the hydrophobic cores and the binding site loops, suggests that none of them are crucial for either the formation or the stability of the fold, but are required to generate diversity and specificity to particular carbohydrates. In contrast, the presence of the three sheets in a particular geometry and also their topological connectivities seem to be important. The fold has been shown to tolerate different types of protein-protein associations, most of them exhibiting different types of quaternary associations and some even existing as complexes with other folds. The function of every family in this study is discussed with respect to its fold, leading to the suggestion that this fold can be linked to carbohydrate recognition in general.

Sequencing of the complete genome of Mycobacterium tuberculosis, combined with the rapidly increasing need to improve tuberculosis management through better drugs and vaccines, has initiated extensive research on several key proteins from the pathogen. RecA, a ubiquitous multifunctional protein, is a key component of the processes of homologous genetic recombination and DNA repair. Structural knowledge of MtRecA is imperative for a full understanding of both these activities and any ensuing application. The crystal structure of MtRecA, presented here, has six molecules in the unit cell forming a 6(1) helical filament with a deep groove capable of binding DNA. The observed weakening in the higher order aggregation of filaments into bundles may have implications for recombination in mycobacteria. The structure of the complex reveals the atomic interactions of ADP-AlF(4), an ATP analogue, with the P-loop-containing binding pocket. The structures explain reduced levels of interactions of MtRecA with ATP, despite sharing the same fold, topology and high sequence similarity with EcRecA. The formation of a helical filament with a deep groove appears to be an inherent property of MtRecA. The histidine in loop L1 appears to be positioned appropriately for DNA interaction.