Staphylococcus epidermidis is an opportunistic pathogen and a major cause of foreign body infections. The S. epidermidis fibrinogen (Fg)-binding adhesin SdrG is necessary and sufficient for the attachment of this pathogen to Fg-coated materials. Based largely on structural analyses of the ligand binding domain of SdrG as an apo-protein and in complex with a Fg-like peptide, we proposed that SdrG follows a "dock, lock, and latch" mechanism to bind to Fg. This binding mechanism involves the docking of the ligand in a pocket formed between two SdrG subdomains followed by the movement of a C-terminal extension of one subdomain to cover the ligand and to insert and complement a ␤-sheet in a neighboring subdomain. These proposed events result in a greatly stabilized closed conformation of the MSCRAMM-ligand complex. In this report, we describe a biochemical analysis of the proposed conformational changes that SdrG undergoes upon binding to its ligand. We have introduced disulfide bonds into SdrG to stabilize the open and closed forms of the apoform of the MSCRAMM. We show that the stabilized closed form does not bind to the ligand and that binding can be restored in the presence of reducing agents such as dithiothreitol. We have also used Förster resonance energy transfer to dynamically show the conformational changes of SdrG upon binding to its ligand. Finally, we have used isothermic calorimetry to determine that hydrophobic interactions between the ligand and the protein are responsible for re-directing the C-terminal extension of the second subdomain required for triggering the ␤-strand complementation event.The attachment of microbes to host tissues represents the initial step in the pathogenesis of most infections, with specificity and tissue tropism being defined by precise adhesin-ligand interactions. For bacteria that are not obligatory intracellular pathogens, extracellular matrix proteins appear to be preferred targets for bacterial adhesion. The adhesins mediating these interactions have been termed MSCRAMMs (microbial surface components recognizing adhesive matrix molecules).2 Multiple MSCRAMMs have been found in many organisms. On Gram-positive bacteria, a family of MSCRAMMs might have arisen from a common ancestor, as indicated by their amino acid sequence relatedness, similar modular design, and common binding domain organization. In general, these structurally related MSCRAMMs (Fig. 1A) contain an N-terminal ϳ40 amino acid long signal sequence (S), and C-terminal features that are required for sorting the proteins to the cell wall including a proline-rich wall-spanning region (W), the wall anchoring LPXTG motif, a hydrophobic transmembrane region (M), and a positively charged cytoplasmic tail (C). The ligand binding activity of most of these MSCRAMMs is localized to the N-terminal A regions, which in the staphylococcal proteins are ϳ500 amino acids long.The blood plasma protein fibrinogen is targeted by many MSCRAMMs. In the cases of Staphylococcus epidermidis and Staphylococcus aureus, fibrinogen-bin...

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The article presents the full version of the NOVGOST computer program for determining the effective contact and bending phase criterional stresses of Novikov gearing teeth with basic profile according to GOST 15023–76, developed in the system MAPLE 17. The program reproduces the process of real multipoint engagement of Novikov gearing, which takes into account the inevitable errors in the manufacture and assembly of a gear pair, dependent on the assigned degree of accuracy, as well as the rigidity of the teeth themselves and the associated parts of the gearbox – shafts and bearings. The program is based on the results of solving a 3D contact problem to determine the phase dependences of the effective contact and bending stresses, as well as rigidity of teeth from the ends of the teeth, when the contact area is positioned anywhere along the length of the tooth, including the end of gear rim, taking into account the influence of the latter on the listed parameters through the coefficients of influence. With the help of the presented program partial forces in real multipoint engagement are determined, acting on each contact area and, In this way, phase criterional stress are calculated, determining the load-bearing capacity and service life of Novikov՚s gearing. The program laid the opportunity to set the parameter of the longitudinal modification of the teeth, optimal selection of which allows significantly reduce the criterional stress and thereby significantly improve working capacity projected gearing. The program can be very useful for designing and manufacturing in production competitive in the global market gearboxes with high technical economic indicators, equipped with Novikov gearing.