Cavities on a proteins surface as well as specific amino acid positioning within it create the physicochemical properties needed for a protein to perform its function. CASTp () is an online tool that locates and measures pockets and voids on 3D protein structures. This new version of CASTp includes annotated functional information of specific residues on the protein structure. The annotations are derived from the Protein Data Bank (PDB), Swiss-Prot, as well as Online Mendelian Inheritance in Man (OMIM), the latter contains information on the variant single nucleotide polymorphisms (SNPs) that are known to cause disease. These annotated residues are mapped to surface pockets, interior voids or other regions of the PDB structures. We use a semi-global pair-wise sequence alignment method to obtain sequence mapping between entries in Swiss-Prot, OMIM and entries in PDB. The updated CASTp web server can be used to study surface features, functional regions and specific roles of key residues of proteins.

Computed Atlas of Surface Topography of proteins (CASTp) provides an online resource for locating, delineating and measuring concave surface regions on three-dimensional structures of proteins. These include pockets located on protein surfaces and voids buried in the interior of proteins. The measurement includes the area and volume of pocket or void by solvent accessible surface model (Richards' surface) and by molecular surface model (Connolly's surface), all calculated analytically. CASTp can be used to study surface features and functional regions of proteins. CASTp includes a graphical user interface, flexible interactive visualization, as well as on-the-fly calculation for user uploaded structures. CASTp is updated daily and can be accessed at http://cast.engr.uic.edu.

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Surface (S)-layers, para-crystalline arrays of protein, are deposited in the envelope of most bacterial species. These surface organelles are retained in the bacterial envelope through the non-covalent association of proteins with cell wall carbohydrates. Bacillus anthracis, a Gram-positive pathogen, produces S-layers of the protein Sap, which uses three consecutive repeats of the surface-layer homology (SLH) domain to engage secondary cell wall polysaccharides (SCWP). Using x-ray crystallography, we reveal here the structure of these SLH domains, which assume the shape of a three-prong spindle. Each SLH domain contributes to a three-helical bundle at the spindle base, whereas another ␣-helix and its connecting loops generate the three prongs. The inter-prong grooves contain conserved cationic and anionic residues, which are necessary for SLH domains to bind the B. anthracis SCWP. Modeling experiments suggest that the SLH domains of other S-layer proteins also fold into three-prong spindles and capture bacterial envelope carbohydrates by a similar mechanism.Surface layers (S-layers) 3 are para-crystalline sheets of protein, which self-assemble on the surface of microbial cells to form contiguous layers (1, 2). Most organisms that elaborate S-layers do so by abundantly producing and secreting a single protein species (3). Whether an organism produces an S-layer as a component of its envelope structure is assessed by electron microscopy of the cell surface (4). In this manner, species from nearly every branch of the Bacteria and Archaea have been discovered to produce S-layers (2). Proteins within S-layers fulfill variable functions in that they act either as a scaffold or enzyme in the bacterial envelope (5), promote nutrient diffusion or transport (6), or contribute to virulence by enabling microbial adhesion to infected host tissues (7).Most, but not all, S-layer proteins of bacteria share three tandem ϳ55 amino acid repeats of the Surface Layer Homology (SLH) domain (8 -10). Secreted proteins encoding three tandem SLH domains are tethered to the bacterial envelope by non-covalent interactions between the SLH domains and a secondary cell wall carbohydrate (11). SLH domains are remarkable for being both necessary and sufficient for the incorporation of chimeric proteins into S-layers (12, 13). The SbsC protein of Geobacillus stearothermophilus is an example for a class of protein that forms S-layers without SLH domains (14). SbsC binds to the secondary cell wall polysaccharide (SCWP) of G. stearothermophilus via its N-terminal domain, which consists of three triple-helical bundles that are connected by two contiguous helices (14). The N-terminal domain of SbsC has high similarity with S-layer proteins from G. stearothermophilus, Geobacillus kaustophilus, and Geobacillus tepidamans (14) and is not similar to proteins with SLH domains.The Gram-positive bacterium Bacillus anthracis is a rodshaped, spore-forming pathogen of mammalian hosts (15). The envelope of its vegetative forms is composed of a plasma membrane a...