Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An anticoagulant protein, factor IX/factor X-binding protein (IX/X-bp), isolated from the venom of Trimeresurus flavoviridis, binds with factor IX and factor X in the presence of Ca2+ with a 1 to 1 stoichiometry (Atoda, H., and Morita, T. (1989) J. Biochem. (Tokyo) 106, 808-813). Analysis of S-pyridylethylated IX/X-bp by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a 16.0-kDa band (designated the A chain) and a 15.5-kDa band (designated the B chain). These two chains were separated by reversed-phase high performance liquid chromatography, and their complete amino acid sequences were determined by sequencing of the peptides obtained after digestion with lysyl endopeptidase, chymotrypsin, and V8 protease from Staphylococcus aureus and after chemical cleavage with cyanogen bromide. The A chain had an amino-terminal sequence of Asp-Cys-Leu-Ser-Gly- and consisted of 129 residues with Mr 14,830. The B chain has an amino-terminal sequence of Asp-Cys-Pro-Ser-Asp- and consists of 123 residues of Mr 14,440. There was 47% identity between the A and the B chain. The sequence of IX/X-bp showed 25-37% identity with that of the C-type carbohydrate recognition domain-like structure of acorn barnacle lectin, human and rat asialoglycoprotein receptors, the human lymphocyte Fc epsilon receptor for immunoglobulin E, proteoglycan core protein, pancreatic stone protein, and tetranectin. The sequences of the first 18 amino acid residues of both the A and B chains were also, to a certain extent, homologous to the partial amino acid sequence of the b subunit of factor XIII, a member of the beta 2-glycoprotein I-like family. In this region, some similarity with the amino-terminal amino acid sequence of botrocetin was also observed.
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PMID:The primary structure of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Homology with asialoglycoprotein receptors, proteoglycan core protein, tetranectin, and lymphocyte Fc epsilon receptor for immunoglobulin E. 183 Nov 97

Different proteins, even without sequence similarity, still can contain similar surface regions involved in protein-protein interactions with common target. These regions can serve as structural determinants of cross-reactivity and molecular mimicry. Molecular mimicry, defined as the process in which structural properties of one molecule are simulated by the dissimilar molecules, is implicated in several biologically important processes, including autoimmune and allergic reactions, binding of some ligands to common receptor, and interactions in cell signaling. The problem of identification of the determinants of molecular mimicry is not completely solved at this time. We hypothesize that identification of structurally and chemically similar surface regions of two protein molecules capable of binding to the same target will allow us to identify sites involved in cross-reactivity including determinants of the molecular mimicry. We used a graph-theoretical approach in order to determine highly similar surface regions of two proteins with known three-dimensional structures. This approach uses a variation of Maximal Common Subgraph (MCS) isomorphism, where an association graph is constructed based on the surface-exposed residues of the two molecules and the matching regions are found based on the maximum cliques in the association graph. Testing the proposed method on the targets of autoantibody involved in antiphopholipid syndrome (APS)--beta2-GPI, PC, thrombin, factor IX, factor X, and plasmin allowed identifying potential epitopes for antibody that can inhibit coagulation proteases. Application of this method to the Activated Protein C and factor VII Gla-domains revealed surface regions involved in EPCR and plasma membrane binding, consistent with known experimental results. Analysis of major pollen allergen that can cause food allergies through cross-reactivity found known epitopes involved in cross-reactivity and also revealed additional surface regions that can complement the list of epitopes. Taken together, our results suggest that the proposed graph-theoretical approach can identify determinants of cross-reactivity and molecular mimicry.
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PMID:Graph-theoretical comparison of protein surfaces reveals potential determinants of cross-reactivity and the molecular mimicry. 1993 50