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The 2.8 Å resolution three-dimensional structure of a complex between an antigen (lysozyme) and the Fab fragment from a monoclonal antibody against lysozyme has been determined and refined by x-ray crystallographic techniques. No conformational changes can be observed in the tertiary structure of lysozyme compared with that determined in native crystalline forms. The quaternary structure of Fab is that of an extended conformation. The antibody combining site is a rather flat surface with protuberances and depressions formed by its amino acid side chains. The antigen-antibody interface is tightly packed, with 16 lysozyme and 17 antibody residues making close contacts. The antigen contacting residues belong to two stretches of the lysozyme polypeptide chain: residues 18 to 27 and 116 to 129. All the complementarity-determining regions and two residues outside hypervariable positions of the antibody make contact with the antigen. Most of these contacts (10 residues out of 17) are made by the heavy chain, and in particular by its third complementarity-determining region. Antigen variability and antibody specificity and affinity are discussed on the basis of the determined structure.

Predictions of the structures of the antigen-binding domains of an antibody, recorded before its experimental structure determination and tested subsequently, were based on comparative analysis of known antibody structures or on conformational energy calculations. The framework, the relative positions of the hypervariable regions, and the folds of four of the hypervariable loops were predicted correctly. This portion includes all residues in contact with the antigen, in this case hen egg white lysozyme, implying that the main chain conformation of the antibody combining site does not change upon ligation. The conformations of three residues in each of the other two hypervariable loops are different in the predicted models and the experimental structure.

By using X-ray diffraction and immunochemical techniques, we have exploited the use of monoclonal antibodies raised against hen egg lysozyme (HEL) to study systematically those factors responsible for the high specificity of antigen-antibody interactions. HEL was chosen for our investigations because its three-dimensional structure and immunochemistry have been well characterized and because naturally occurring sequence variants from different avian species are readily available to test the fine specificity of the antibodies. The X-ray crystal structure of a complex formed between HEL and the Fab D1.3 shows a large complementary surface with close interatomic contacts between antigen and antibody. Thus single amino acid sequence changes in heterologous antigens give antigen-antibody association constants that are several orders of magnitude smaller than that of the homologous antigen. For example, a substitution of His for Glu at position 121 in the antigen is sufficient to diminish significantly the binding between D1.3 and the variant lysozyme. The conformation of HEL when complexed to D1.3 shows no significant difference from that seen in the free molecule, and immunobinding studies with other anti-HEL antibodies suggest that this observation may be generally true for the system of monoclonal antibodies that we have studied.

CELLULOSIC biomass is recycled by a variety of microorganisms occupying different habitats 1 . Studies of their cellulase systems have included the purification of enzyme components, the determination of their enzymological properties 2 and the cloning and characterization of their structural genes 3 . Sequence analysis of more than 70 cellulases permits grouping into seven families corresponding to distinct structural types 4,5 . The three-dimensional structure of the catalytic core of cellobiohydrolase CBHII from the fungus Trichoderma reesei has been reported 6 . Here we show that endoglucanase CelD from Clostridium thermocellum , which is representative of a different family of cellulose-degrading enzymes consisting of at least 11 bacterial, fungal and plant endoglucanases 5,7 , has a globular structure, with an amino-terminal immunoglobulin-like domain tightly packed against a larger catalytic domain. The latter shows a novel protein fold, shaped like an α-barrel of 12 helices connected by loops that form the active site. The structure of a complex CelD with a substrate analogue suggests a mechanism for substrate hydrolysis.

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The 2.8 angstroms resolution three-dimensional structure of a complex between an antigen (lysozyme) and the Fab fragment from a monoclonal antibody against lysozyme has been determined and refined by x-ray crystallographic techniques. Antigen variability and antibody specificity and affinity are discussed on the basis of the determined structure.

The 2.8 angstrom resolution three-dimensional structure of a complex between an antigen (lysozyme) and the Fab fragment from a monoclonal antibody against lysozyme has been determined and refined by X-ray crystallographic techniques.

By using X -ray diffraction and immunochemical techniques, we have exploited the use of monoclonal antibodies raised against hen egg lysozyme (HEL) to study systematically those factors responsible for the high specificity of antigen -antibody interactions. HEL was chosen for our investigations because its three-dimensional structure and immunochemistry have been well characterized and because naturally occurring sequence variants from different avian species are readily available to test the fine specificity of the antibodies. The X-ray crystal structure of a complex formed between HEL and the Fab D1.3 shows a large complementary surface with close interatomic contacts between antigen and antibody. Thus single amino acid sequence changes in heterologous antigens give antigen-antibody association constants that are several orders of magnitude smaller than that of the homologous antigen. For example, a substitution of His for Glu at position 121 in the antigen is sufficient to diminish significantly the binding between D1.3 and the variant lysozyme. The conformation of HEL when complexed to D1.3 shows no significant difference from that seen in the free molecule, and immunobinding studies with other anti-HEL antibodies suggest that this observation may be generally true for the system of monoclonal antibodies that we have studied.

Initial treatment of paroxysmal atrial fibrillation with cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation and other atrial tachyarrhythmias over 3 years than rhythm-control medications.

Surveillance for hepatocellular carcinoma (HCC) has level I evidence among patients with hepatitis B but only level II evidence in patients with cirrhosis. This lack of randomized data has spurred questions regarding the utility of HCC surveillance in this patient population; however, lack of randomized data does not equate to a lack of data supporting the efficacy of surveillance. The aim of our study was to determine the effect of HCC surveillance on early stage tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis. We performed a systematic literature review using Medline from January 1990 through January 2014 and a search of national meeting abstracts from 2009-2012. Two investigators identified studies that reported rates of early stage tumor detection, curative treatment receipt, or survival, stratified by HCC surveillance status, among patients with cirrhosis. Both investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for a random effects model. We identified 47 studies with 15,158 patients, of whom 6,284 (41.4%) had HCC detected by surveillance. HCC surveillance was associated with improved early stage detection (odds ratio [OR] 2.08, 95% CI 1.80-2.37) and curative treatment rates (OR 2.24, 95% CI 1.99-2.52). HCC surveillance was associated with significantly prolonged survival (OR 1.90, 95% CI 1.67-2.17), which remained significant in the subset of studies adjusting for lead-time bias. Limitations of current data included many studies having insufficient duration of follow-up to assess survival and the majority not adjusting for liver function or lead-time bias. HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis. Please see later in the article for the Editors' Summary.