Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that tissue-type plasminogen activator (t-PA) in blood is cleared by the liver partially through a mannose-specific uptake system. The present study was undertaken to investigate, in a purified system, whether t-PA is recognized by the mannose receptor which is expressed on macrophages and liver sinusoidal cells. The mannose receptor was isolated and purified from bovine alveolar macrophages and migrated as a single protein band at Mr 175,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Ligand blotting revealed that this protein specifically bound t-PA. The t-PA-receptor interaction was further characterized in a binding assay, which showed saturable binding with an apparent dissociation constant of 1 nM. t-PA binding required calcium ions and was negligible in the presence of EDTA or at acid pH. Mannose-albumin was an effective inhibitor, whereas galactose-albumin did not have a significant effect. From a series of monosaccharides tested, D-mannose and L-fucose were the most potent inhibitors, N-acetyl-D-glucosamine was a moderate inhibitor, whereas D-galactose and N-acetyl-D-galactosamine were ineffective. t-PA, deglycosylated by endoglycosidase H, did not interact with the receptor. It is concluded that the mannose receptor specifically binds t-PA, probably through its high mannose-type oligosaccharide.
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PMID:Binding of tissue-type plasminogen activator by the mannose receptor. 190 88

We deduced that Agkistrodon actus venom serine proteinases I and II, previously isolated from the venom of A. acutus (Zhu, Z., Gong, P., Teng, M., and Niu, L. (2003) Acta Crystallogr. Sect. D Biol. Crystallogr. 59, 547-550), are encoded by two almost identical genes, with only the single substitution Asp for Asn at residue 62. Amidolytic assays indicated that they possess slightly different enzymatic properties. Crystal structures of A. actus venom serine proteinases I and II were determined at resolution of 2.0 and 2.1 A with the identification of trisaccharide (NAG(301)-FUC(302)-NAG(303)) and monosaccharide (NAG(301)) residues in them, respectively. The substrate binding sites S3 of the two proteinases appear much shallower than that of Trimeresurus stejnegeri venom plasminogen activator despite the overall structural similarity. Based on structural analysis, we showed that these Asn(35)-linked oligosaccharides collide spatially with some inhibitors, such as soybean trypsin inhibitor, and would therefore hinder their inhibitory binding. Difference of the carbohydrates in both the proteinases might also lead to their altered catalytic activities.
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PMID:Crystal structures and amidolytic activities of two glycosylated snake venom serine proteinases. 1563 14

In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.
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PMID:Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. 1651 Jan 78