Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The net percentage of release of arylsulfatase activity from purified rat mast cells induced by rabbit anti-rat F(ab')2 was consistently only about 1/3 that of histamine. Isoelectric focusing of the released and residual arylsulfatase activities demonstrated specific release of the A type without B and a net percentage of immunologic release of arylsulfatase A equivalent to that of histamine. When the net percentage of histamine and arylsulfatase A release were nearly maximal (88 and 76%) in response to the calcium ionophore A23187, specific release of arylsulfatase B did not occur. Thus, arylsulfatase A and not B was associated with the secretory granule released from the rat mast cell by reversed anaphylaxis or the calcium ionophore. In contrast, subcellular fractionation of water-lysed mast cells yielded arylsulfatase B with the heparin- and chymase-containing granule fraction and arylsulfatase A in the aqueous fraction comprised of cell sap and granule water eluate. It may be that arylsulfatase B resides in a minor second granule, whereas arylsulfatase A is loosely associated with the predominant secretory granule of the rat mast cell.
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PMID:Release of arylsulfatase A but not B from rat mast cells by noncytolytic secretory stimuli. 8 Dec 31

Rat mast cell granules contain a spectrum of enzymes as established by histochemical techniques and subcellular fractionation. However, 35% of the beta-glucuronidase, 30% of the beta-D-galactosidase, 14% of the beta-hexosaminidase and all of the acid phosphatase is not available for immunologic release from purified rat serosal mast cells, suggesting the presence of nonsecretory lysosomes containing these acid hydrolases. On the other hand, immunologic release of the majority of chymase, beta-hexosaminidase, beta-glucuronidase, beta-D-galactosidase, and arylsulfatase A occurs in parallel with histamine and thereby localizes these substances to the rat mast cell secretory granule. A molecular model of the secretory granule in the resting mast cell can now be constructed in which heparin proteoglycan is the granule matrix to which chymase and probably other proteins are ionically bound. Inhibition of chymase by serotonin stored in its active site and of chymase and acid hydrolases by their interaction with heparin probably occurs. Histamine is stored by ionic linkage to carboxyl groups of protein and heparin. Micromolar amounts of heparin glycosaminoglycans, histamine, serotonin, chymase, beta-D-hexosaminidase, beta-glucuronidase, and arylsulfatase A in secretory granules of 10(6) mast cells are 0.7--1.3 x 10(-3), 70--220 x 10(-3), 0.9--28 x 10(-3), 0.2--0.5 x 10(-3), 0.9--2.7 x 10(-6), 0.1--0.3 x 10(-6) and less than 8 x 10(-6), respectively. In addition, the total protein available for calcium ionophore-induced release from 10(6) rat mast cells is about 60 microgram, indicating that less than 50% of the granule protein can be accounted for. Recognition that mast cell secretory granules contain acid hydrolases indicates that they are modified lysosomes; their special intracellular and extracellular functions are dictated by the associated novel constituents and the stimulus for activation.
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PMID:Enzymes of the mast cell granule. 677 34

Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HN-SO2-NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications.
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PMID:Therapeutic potential of sulfamides as enzyme inhibitors. 1671 Aug 59

The sulfamide moiety, similarly to the structurally related sulfonamide and sulfamate ones, is widely employed in medicinal chemistry for the design of biologically active compounds. Amongst the enzymes for which sulfamide-based inhibitors were designed are the carbonic anhydrases (CAs), and a large number of proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase), serine protease (elastase, chymase, tryptase and thrombin, among others) and metalloproteinase (carboxypeptidase A [CPA] and matrix metalloproteinase [MMP]) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays an important role in the binding of the inhibitor to the active site cavity. This is achieved either by directly coordinating to the metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or, as in the case of the cyclic sulfamides, acting as HIV protease inhibitors interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HN-SO(2)-NH motif that substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physicochemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability etc., due to the intrinsic properties of this highly polarised moiety when attached to an organic scaffold. This interesting motif is, thus, of great value for the design of pharmacological agents with many applications.
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PMID:The sulfamide motif in the design of enzyme inhibitors. 2014 8