The human mannose-binding protein (MBP)' is an acute phase serum protein of -300 kD comprised of multimers of a 32-kD subunit (1-3). It is a member of an ever-growing family of animal lectins that share at least 18 invariant residues in their carbohydrate recognition domain (CRD). The family can be divided into membrane proteins and soluble proteins, and all bind ligands optimally at neutral pH in the presence of calcium (reviewed in reference 4). For membrane proteins, the CRD is attached to a membrane anchor domain as found in the asialoglycoprotein receptors of rat (5) and human (6, 7), the chicken hepatic lectin (8), the lymphocyte IgE Fc receptor (9), and a rat Kupffer cell-binding protein (10) . This group has recently been expanded to include a lymphocyte homing receptor (11), a granular membrane protein of platelets and endothelium, GMP-140 (12), and ELAM-1, a cytokine-inducible endothelial cell receptor (13) . The function of the attachment domains of the soluble lectins, which include MBP (14, 15), the apoprotein of pulmonary surfactant SP-A (16, 17), cartilage proteoglycan core protein (18), a fly (19) and sea urchin lectin (20), and an acorn barnacle lectin (21) are not known_ Only in the rat and human MBP, and dog, human, and rabbit (22) surfactant A protein, are the noncarbohydrate recognition domains similar. In these proteins there is a collagen-like region that is preceded by a cysteine-rich NH2-terminal region that mediates interchain disulphide bonds. As our knowledge of the function of MBP and surfactant A protein expands, it appears that each domain of these proteins may have a defined purpose.Until recently, the function of MBP was not known. However, a function in host defense is suggested by its ability to bind yeast manvans (1) and interact with the complement cascade (23), and by our finding that MBP prevents infection of H9 lymphoblasts by HIV by binding to the high mannose glycans expressed on the
Mannose-binding proteins have been isolated from the liver of rats and humans and subsequently been found in the serum of rats, rabbits, and humans. We report the isolation of cDNA clones isolated from a human liver cDNA library that encodes a human mannose-binding protein. The primary structure has three domains: (a) an NH2-terminal cysteine-rich segment of 19 amino acids which appears to be involved in the formation of interchain disulfide bonds that would stabilize multimeric forms of the protein; (b) a collagen-like region consisting of 19 repeats of the sequence Gly-x-y; and (c) a COOH-terminal putative carbohydrate-binding domain consisting of 148 residues. This human mannose-binding protein bears 51% overall homology (allowing three gaps) with a rat mannose-binding protein C and 48% homology (allowing seven gaps) with a rat mannose-binding protein A. Like these homologous rat proteins, the human mannose-binding protein COOH-terminal sequences are homologous to the carbohydrate recognition portion of several other lectin-like proteins including mammalian hepatic receptors, an insect-soluble hemolymph, and a sea urchin lectin found in coelomic fluid. The apoproteins of dog and human surfactant and the human lymphocyte IgE Ec receptor have not been shown to have lectin-like properties, yet by homology are members of this family of lectin-like proteins. The human mannose-binding protein is preceded by a typical hydrophobic signal sequence and its hepatic secretion is induced as part of the acute-phase response consistent with its probable role in host defense.
Staff training on diversity issues is required to encourage institutional buy-in and establish consistent educational and clinical environments. By tackling cultural diversity within the context of patient-centred care, cultural humility, the approach students valued most, would become the default model. Reflective practice and the development of a critical consciousness are crucial in the improvement of cultural diversity training and thus should be facilitated and encouraged. Educators can adopt a bidirectional mode of teaching and work with students to decolonise medical curricula and improve medical practice.
The biosynthesis of monensin by Streptomyces cinnamonensis was studied by using '4C-labeled glucose, acetate, propionate, butyrate, and methionine. The results indicated that the antibiotic is synthesized from five acetate, seven propionate, and one butyrate molecules. The o-methyl group of monensin is derived from methionine, whereas the terminal hydroxymethyl group is incorporated from acetate.Monensin, an antibiotic produced by Streptomyces cinnamonensis (ATCC 15413), was first described by investigators from Eli Lilly and Co. (4). Initial fermentation studies were presented by Stark (7). The structure of the major component, factor A (Fig. 1), was determined by X-ray crystallographic analysis of the silver salt by Agtarap et al. (2). In addition to factor A, three additional factors have been recognized (3): in factor B the ethyl group on ring C is replaced by a methyl group, in factor C the methyl at the carboxyl end is replaced by an ethyl group, and in factor D the methyl group on the B ring is replaced by an ethyl group. The structures of factors C and D are tentative proposals. Factors B, C, and D are minor constituents of the fermentation broth. Factor A, hereafter designated monensin, and its sodium salt are only slightly soluble in water but are very soluble in organic solvents.This study is concerned with the biosynthesis of monensin and the incorporation of labeled intermediates into the antibiotic. MATERIALS AND METHODSOrganism and cultural conditions. The ingredients of the medium used during these studies with S. cinnamonensis, ATCC 15413, were (in mg/ml): glucose (16.7), L-tyrosine (3.3), L-valine (6.6), L-lysine (1.0), CaCO, (1.0), FeSO4 7H20 (0.17), K2HPO4 (0.17), KCl (0.05), MgSO4 7H20 (0.67), biotin (0.025), and folic acid (0.025). Cultures were grown at 32 C in shaken (250 rpm) flasks (100 ml of medium per 500 ml wide-mouth flask), or in 1. Isolation of monensin. The whole broth was harvested and the pH was adjusted to 9.0 with NaOH, after which it was extracted twice with one-half volume of chloroform. The extracts were combined and washed through a column containing carbon (Pittsburgh 12 by 40 mesh). The column was washed with excess chloroform, and the combined extracts were evaporated. The residue was dissolved in methanol and chilled. Cold deionized water was added until the monensin crystallized. The monensin was collected by filtration, washed with cold water, recrystallized from petroleum ether, and assayed for radioactivity.Degradation of labeled monensin. The periodate oxidation of monensin is illustrated in Fig. 2. A sample of "4C-labeled monensin (100 mg) was dissolved in t-butanol (4 ml) with stirring. To 'this solution was added 0.2 M aqueous sodium meta-periodate solution (2 ml). The final mixture was allowed to stand overnight. The reaction mixture was distilled into a receiver containing a dimedone solution (100 mg of dimedone in 2 ml of 50% ethanol-water). The distillate was allowed to stand a few minutes and then concentrated under reduced pressure to induce crystallizat...
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