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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyspecific natural autoantibodies (NAAb) are antibodies present in normal unimmunized animals and are able to react with very dissimilar antigens (Ag). To better delineate the characteristics of polyspecificity, we subjected monoclonal NAAb to four different immunochemical studies: (1) Two-dimensional gel electrophoresis performed on eight NAAb did not reveal any obvious relationship between charge and antigen specificities; (2) NAAb widely polyspecific on proteins and nucleic acid were reactive with lipids bearing either phosphate, sulfate or carboxyl polar groups; (3) pepsin digestion of polyspecific IgM NAAb yielded Fab'2 fragments which maintained their multireactivities, but exhibited a decrease in reactivity as compared to that seen with monospecific mAb (induced); (4) two different assays were used to analyse the complement fixation ability of IgM NAAb. While very weak or no complement fixation was observed with a classical complement fixation test (fluid phase), when a complement enzyme immunoassay was used where Ag is immobilized on a solid phase, polyspecific NAAb fixed reproducible and easily detectable amounts of complement.
Mol Immunol 1988 Oct
PMID:Immunochemical studies of polyspecific natural autoantibodies: charge, lipid reactivity, Fab'2 fragments activity and complement fixation. 321 72

A mouse monoclonal antibody (IgG1 isotype) against human C1q (MAb 130) is presented that activates C1 in serum through its antigen-binding sites at an optimal molar ratio of 3 MAbs:1 C1q. The antibody does not inhibit binding of C1q to IgG. Experiments with pepsin- and collagenase-digested C1q showed that MAb 130 binds to the fibril-like strands (arms) of C1q, close to the globular heads. Bivalency of MAb 130 was a requirement for C1-activation, but not for binding to C1q. Increasing the segmental flexibility of the intact antibody by reduction and alkylation destroyed its capacity to activate C1. A MAb against the globular heads of C1q completely inhibited C1-activation by aggregated IgG (AHG), but did not prevent activation by MAb 130. C1, reconstituted by adding C1q-stalks that lack the globular heads to C1q-depleted serum was not activated by AHG, whereas activation by MAb 130 was not affected. Activation of serum-C1 by AHG and MAb 130 was inhibited by addition of excess purified C1-inhibitor in a comparable and dose-dependent manner. Sucrose-gradient analysis indicated a predominance of stable complexes of a single C1q-molecule with three MAbs at the optimal activating ratio. When isolated and added to C1q-depleted serum, these complexes activated C1 efficiently. A mechanism for activation by MAb 130 is proposed that supports the "distortive" model of C1-activation.
Mol Immunol 1988 May
PMID:The distortive mechanism for the activation of complement component C1 supported by studies with a monoclonal antibody against the "arms" of C1q. 326 34

Aspartic proteases (EC3.4.23) are a group of proteolytic enzymes of the pepsin family that share the same catalytic apparatus and usually function in acid solutions. This latter aspect limits the function of aspartic proteases to some specific locations in different organisms; thus the occurrence of aspartic proteases is less abundant than other groups of proteases, such as serine proteases. The best known sources of aspartic proteases are stomach (for pepsin, gastricsin, and chymosin), lysosomes (for cathepsins D and E), kidney (for renin), yeast granules, and fungi (for secreted proteases such as rhizopuspepsin, penicillopepsin, and endothiapepsin). These aspartic proteases have been extensively studied for their structure and function relationships and have been the topics of several reviews or monographs (Tang: Acid Proteases, Structure, Function and Biology. New York: Plenum Press, 1977; Tang: J Mol Cell Biochem 26:93-109, 1979; Kostka: Aspartic Proteinases and Their Inhibitors. Berlin: Walter de Gruyter, 1985). All mammalian aspartic proteases are synthesized as zymogens and are subsequently activated to active proteases. Although a zymogen for a fungal aspartic protease has not been found, the cDNA structure of rhizopuspepsin suggests the presence of a "pro" enzyme (Wong et al: Fed Proc 44:2725, 1985). It is probable that other fungal aspartic proteases are also synthesized as zymogens. It is the aim of this article to summarize the major models of structure-function relationships of aspartic proteases and their zymogens with emphasis on more recent findings. Attempts will also be made to relate these models to other aspartic proteases.
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PMID:Evolution in the structure and function of aspartic proteases. 354 46

The electrophoretic mobilities of the collagen and procollagen type I and III chains synthesized by the fibroblasts isolated from patients with type I Ehlers-Danlos syndrome as well as a set of peptides obtained by splitting of pro alpha 1(I) and pro alpha 2(I) type I procollagens by cyanbromide are not different from the normal ones. The fact demonstrates the absence of long insertions or deletions, or the sufficient defects in intracellular chain modifications. The changes were also nor registered for the ratio of type I and III collagens from the digested by pepsin preparations of protein accumulating in the culture media of the cultured skin fibroblasts from patients. The studied strains of cultured fibroblasts from patients suffering the Ehlers-Danlos syndrome have the trend to increased accumulation of partially processed chains of proc alpha 1(I) and proc alpha 2(I) type I procollagen and to the increased ratio of pro alpha 1(I) to pro alpha 2(I).
Mol Gen Mikrobiol Virusol 1987 Jan
PMID:[Various characteristics of the structure and synthesis of procollagens produced by cultured skin fibroblasts from patients with Danlos-Ehlers syndrome type I]. 356 22

Three commercial preparations of immunoglobulin G prepared for administration by the i.v. route were tested for their physical integrity and in vitro biological activity. Size exclusion chromatography by HPLC in native and denaturing buffers together with SDS-PAGE analysis were used to determine whether covalent-bond cleavage had occurred as a result of procedures used in their preparation. C1 complement binding assays and measurements of competitive binding to an Fc receptor-bearing promonocyte cell line U937 were used to assess whether such changes had altered the capacity of these preparations to engage biological effector functions. A purified IgG1 myeloma protein was used as a reference standard. WinRho, an unmodified IgG, consisted almost wholly of monomeric IgG by HPLC size exclusion and showed no evidence of proteolytic fragments in denaturing buffers or on SDS-PAGE. Sandoglobulin, a product treated at pH 4 with pepsin, contained about 10% dimeric protein and, as revealed under denaturing conditions, about 2% fragments. Relative affinity of binding to U937 cells was similar to WinRho. C1 binding by Sandoglobulin showed normal activity with 50% inhibition at 2.8 nM. Gamimune, modified by partial reduction and alkylation, contained about 15% dimers. Between 20 and 30% of the preparation retained covalent interchain disulfides. Binding to U937 cells was two-fold weaker than the other preparations and binding to C1 was also diminished and modified. This accords well with previous reports of the deleterious effect of reduction and alkylation on Fc function.
Mol Immunol 1986 Mar
PMID:An examination of the structural and biological properties of three intravenous immunoglobulin preparations. 371 8

Detailed structure of the pepsin active site in the region of the active aspartic acid residues and substrate binding S1 and S1' sites is considered. At the active site of the enzyme crystals studied several molecules of ethanol were detected, which interact with active groups. The catalytic properties of aspartyl proteinases towards dipeptide substrates were explained on the base of the specific structure of S1 and S1' binding sites.
Mol Biol (Mosk)
PMID:[The structure of pepsin. II. Structure of the enzyme active site (at 2 angstroms resolution)]. 392 May 6

This is the first paper in the series of publications on the detailed description of different aspects of pepsin structure. It concerns the domain structure of the enzyme and the topology of the arrangement of beta-strands in pepsin and related aspartic proteases, this topology being quite different from that of all other beta-proteins. The topology, molecular symmetry and the close proximity of the N- and C-termini of domains suggest that at the first stages of evolution polypeptide chains of some preproteins could be closed in rings, which become open at the subsequent stages. Their genes duplicated twice, and the fusion process resulted in a gene consisting of similar parts.
Mol Biol (Mosk)
PMID:[The structure of pepsin. I. Molecular self-symmetry of the enzyme and implications for the evolution of aspartate proteinases]. 392 May 5

The determination of the three dimensional structure of chymosin at 3 A resolution by molecular replacement method is described. The rotation functions for various aspartic proteases were calculated and combined results were used for the refinement of orientational parameters of chymosin molecules in the unit cell. The interpretation of Crowther-Blow translation function map with packing consideration enable to place correctly the molecules in the chymosin unit cell. Several difference Fourier syntheses for chymosin were calculated and differences between pepsin and chymosin structures were detected.
Mol Biol (Mosk)
PMID:[X-ray study of chymosin. I. Molecular replacement at a 3 angstroms resolution]. 392 28

The immunoglobulin-binding capacity of a Peptococcus magnus strain was studied in a sensitive binding assay using purified human immunoglobulin preparations. The P. magnus strain 312 was capable of binding 48% of polyclonal IgG. Twenty-four of 40 purified myeloma proteins (60%) representing immunoglobulin classes A, G and M showed definite reactivity with an uptake level ranging from 45 to 90%. The remaining 16 monoclonal proteins were non-reactive, binding less than 15%. One myeloma protein with antistaphylolysin and two with antistreptolysin O specificity, i.e. monoclonal proteins with defined antigen specificity, were highly reactive. Binding capacity was observed in all four IgG subclasses and in Ig classes A and M. Twenty-three of 27 myeloma proteins of kappa type were reactive but only one of 13 myeloma proteins of lambda type interacted with the P. magnus strain. Isotope-labelled Fab gamma, F(ab')2 gamma and F(ab')2 alpha fragments were effectively bound by the strain. IgG Fc fragments were completely non-reactive. Isolated light immunoglobulin chains inhibited in a dose-dependent way the uptake of intact IgG to bacteria. Purified heavy chains were non-inhibitory. Isotope-labelled antistaphylolysin IgG F(ab')2 fragments preincubated with staphylolysin were as reactive as free antibody fragments, suggesting that the bacterial binding structure is located outside the antibody-combining site. The immunoglobulin reactivity of P. magnus was not affected by heating the bacteria to 80 degrees C for 5 min nor by treatment with trypsin or sodium metaperiodate. Digestion of 2 X 10(9) organisms with 100 micrograms of pepsin and papain reduced the binding by 58 and 90%, respectively. These data indicate that the binding of immunoglobulin to P. magnus is a non-immune reactivity mediated by a heat-stable surface protein interacting with specific sites on the light chain of the immunoglobulin molecule.
Mol Immunol 1985 Aug
PMID:A non-immune interaction between the light chain of human immunoglobulin and a surface component of a Peptococcus magnus strain. 393 Sep 51

Type IV and V collagens were localized in neurofibromas from six patients with von Recklinghausen's neurofibromatosis (NF) using the peroxidase anti-peroxidase (PAP) technique. The collagens were also isolated from neurofibromas by pepsin digestion and fractionating salt precipitations and demonstrated with sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Staining reactions for both collagens were detected in most of the cells in the disorganized NF tumor tissue. These cells also were S-100 protein-positive and were considered to be of Schwannian cell origin, while the type IV collagen-negative cells showed fibroblastoid, mast cell and histiocytic characteristics. Type IV collagen detection was also used to study the structure of a neurofibroma after 3 weeks in tissue culture. The proportion of fibroblastoid, type IV collagen-negative cells increased significantly in the cultured neurofibromas and "buds" containing solely fibroblastoid cells were seen at the periphery of the tumor fragments. Cultured 6th passage tumor cells produced type V but no type IV collagen as estimated with SDS-PAGE. Further, two malignant Schwannomas from a patient with NF were stained with antibodies to type IV collagen. A positive staining reaction was associated only with the vascular walls in the malignant Schwannomas suggesting that type IV collagen expression is linked with cell differentiation. The present data show that the detection of type IV collagen using the PAP-method is useful in studying the organization of tumors with mixed cell populations such as neurofibromas. Large neurofibromas might also serve as a source for the isolation of human type IV and V collagens.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Type IV and V collagens in von Recklinghausen's neurofibromas. An immunohistochemical and electrophoretical study. 615 10


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