Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxamic acids have been reported to be potent and specific inhibitors of urease (EC 3.5.1.5) activity of plant and bacterial origin. The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats. Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9 X 10(-6) M) among nineteen alpha-aminoacyl hydroxamic acids. Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power. The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition. The I50 values of alpha-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids. This fact shows that the alpha-amino group did not affect inhibitory power. However, aspartic-beta-, lysine-, and glutamic-gamma-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or omega-amino group. Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to a higher pH in e presence of an amino group. The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid. Hydroxamic acid inhibits urease activity with strict specificity, excpet for aspartic-beta-hydroxamic acid, which inhibited asparaginase competitively. Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine.
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PMID:Inhibition of urease activity by hydroxamic acid derivatives of amino acids. 23 68

The absorption spectra of trinitrophenyl derivatives of poly(L-lysine) and L-asparaginase undergo irreversible changes in the presence of KBH4. The spectra of trinitrophenyl derivatives of N-acetyl-L-lysine and N-acetyl-L-cysteine are also affected by the addition of the reducing agent. A broad absorption band with a maximum at 426 nm appears in the presence of low concentrations of borohydride with a concomitant decrease in absorbance of the 346 nm band which is characteristic of 1-substituted 2,4,6-trinitrophenyl compounds. In the presence of higher concentrations of KBH4 the long wavelength band becomes less broad as the maximum is shifted to 410 nm and the 346 nm band completely disappears. Similar spectral changes were observed in the presence of Na2SO3 although these were reversible upon removal of the sulfite by dialysis. Based on the spectral similarities with sulfite and hydroxide adducts, we suggest that the 426 nm maximum represents a 1:1 adduct formed between the trinitrophenyl moiety and a hydride ion while the band at 410 nm is assigned to the 1:2 adduct.
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PMID:A spectrophotometric study of the reaction of boro-hydride with trinitrophenyl derivatives of amino acids and proteins. 84 52

The role of amino acids in regulation of L-asparaginase formation was studied in Bacillus mesentericus 43A. Asparagic acid and, to a less extent, asparagine repress biosynthesis of the enzyme. Glutamic acid, glutamine, and other 15 studied amino acids, added separately at a concentration of 10 or 20 mM to the growing culture, have no effect on the activity of the enzyme. Addition of a combination of all 18 amino acids, each at a concentration of 4 mM, to the culture represses the activity by 64%; addition of an acid hydrolysate of lactoalbumin (10 g/litre) represses the activity of the enzyme by 80%. A mixture of amino acids without asparagic acid and asparagine also displays a strong repressing action. Amino acids formed from asparagic acid--lysine, methionine, and isoleucine--do not repress biosynthesis of the enzyme, neither together nor separately. Ammonium nitrogen also does not participate in regulation of asparaginase formation. The cumulative repressing action of amino acids is supposed to be manifested via the mechanism of catabolite repression.
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PMID:[Amino acid regulation of L-asparaginase formation in Bacillus mesentericus]. 93 71

We show that a non-inhibitory monoclonal antibody (MAB) can be selected that provides substantial and sustained protection against proteolytic inactivation of L-asparaginase by trypsin. Of six non-inhibitory, high affinity, monoclonal antibodies to L-asparaginase, one afforded approximately 70% protection. Inactivation of L-asparaginase is associated with a single cleavage adjacent to lysine-29 that results in loss of an N-terminal fragment with a calculated MW of 2,647. The protective MAB prevented this trypsin cleavage. The products of gene fusions of "humanized" fragments of such antibodies and L-asparaginase could have increased clinical utility.
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PMID:Monoclonal antibodies can protect L-asparaginase against inactivation by trypsin. 136 89

A high L-asparaginase (L-asparagine amidohydrolase: EC 3.5.1.1) activity was found under conditions of lysine overproduction in cultures of Corynebacterium glutamicum. L-Asparaginase was purified 98-fold by protamine sulphate precipitation. DEAE-Sephacel anion exchange, ammonium sulphate precipitation and Sephacryl S-200 gel filtration. The asparaginase protein was subjected to PAGE under non-denaturing conditions, identified by an in situ reaction and eluted from the gel in an active form. The estimated Mr from gel filtration and SDS-PAGE was 80,000. The L-asparaginase activity was inhibited by the L-asparagine analogue 5-diazo-4-oxo-L-norvaline. Neither D-asparagine nor L-glutamine was a substrate for the enzyme. L-Asparaginase was produced constitutively: its role may be that of an overflow enzyme, converting excess asparagine into aspartic acid, the direct precursor of lysine and threonine.
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PMID:Characterization and partial purification of L-asparaginase from Corynebacterium glutamicum. 239 90

The L-asparaginase from an extreme thermophile, Thermus aquaticus strain T351, was highly substrate- and stereospecific, with no activity against glutamine or D-asparagine. It had a high Km of 8.6 mM. In these aspects it closely resembled the corresponding enzymes from thermophilic bacteria. The enzyme had a molecular weight of 80,000, an isoelectric point of 4.6, and a pH optimum of 9.5. It showed some substrate inhibition above 20 mM asparagine and was also inhibited by L-aspartic acid, D- and L-lysine (Ki of 5.2 and 1.25 mM, respectively), and D- and L-serine. The half-life of the enzyme at 85 degrees C was 40 min. The Arrhenius plot showed a change in slope at 55 degrees C.
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PMID:A specific L-asparaginase from Thermus aquaticus. 392 88

Administration of either Escherichia coli asparaginase or guinea pig serum to C3H/HE mice with the 6C3HED lymphosarcoma is followed by depression of glycine in the tumor. This decrease in cellular glycine concentration does not occur in a tumor resistant to asparaginase. The inhibition of the lymphosarcoma by asparaginase can be reversed by intraperitoneal injection of asparagine or glycine. This reversal appears to be specific because lysine, threonine, serine, and aspartic acid were ineffective. Loss of cellular glycine may be more important than loss of asparagine because of the requirement for glycine in purine synthesis.
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PMID:Glycine inhibition of asparaginase. 490 4

Procedures are described for linking monomethoxypoly(ethylene glycol) (mPEG) to both epsilon and alpha amino groups of lysine. The lysine carboxyl group can then be activated as a succinimidyl ester to obtain a new mPEG derivative (mPEG2-COOSu) with improved properties for biotechnical applications. This branched reagent showed in some cases a lower reactivity toward protein amino groups than the linear mPEG from which it was derived. A comparison of mPEG- and mPEG2-modified enzymes (ribonuclease, catalase, asparaginase, trypsin) was carried out for activity, pH and temperature stability, Km and Kcat values, and protection to proteolytic digestion. Most of the adducts from mPEG and mPEG2 modification presented similar activity and stability toward temperature change and pH change, although in a few cases mPEG2 modification was found to increase temperature stability and to widen the range of pH stability of the adducts. On the other hand, all of the enzymes modified with the branched polymer presented greater stability to proteolytic digestion relative to those modified with the linear mPEG. A further advantage of this branched mPEG lies in the possibility of a precise evaluation of the number of polymer molecules bound to the proteins; upon acid hydrolysis, each molecule of mPEG2 releases a molecule of lysine which can be detected by amino acid analysis. Finally, dimerization of mPEG by coupling to lysine provides a needed route to monofunctional PEGs of high molecular weight.
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PMID:A branched monomethoxypoly(ethylene glycol) for protein modification. 771 Nov 5

The amino acid sequence and tertiary structure of Wolinella succinogenes L-asparaginase were determined, and were compared with the structures of other type-II bacterial L-asparaginases. Each chain of this homotetrameric enzyme consists of 330 residues. The amino acid sequence is 40-50% identical to the sequences of related proteins from other bacterial sources, and all residues previously shown to be crucial for the catalytic action of these enzymes are identical. Differences between the amino acid sequence of W. succinogenes L-asparaginase and that of related enzymes are discussed in terms of the possible influence on the substrate specificity. The overall fold of the protein subunit is almost identical to that observed for other L-asparaginases. Two fragments in each subunit, a very highly flexible loop (approximately 20 amino acids) that forms part of the active site, and the N-terminus (two amino acids), are not defined in the structure. The orientation of Thr14, a residue probably involved in the catalytic activity, indicates the absence of ligand in the active-site pocket. The rigid part of the active site, which includes the asparaginase triad Thr93-Lys 166-Asp94, is structurally very highly conserved with equivalent regions found in other type-II bacterial L-asparaginases.
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PMID:Crystal structure and amino acid sequence of Wolinella succinogenes L-asparaginase. 889 7

Mammalian tissues contain small form and large form lysophospholipases. Here we report the cloning, sequence, and expression of cDNA encoding the latter form of lysophospholipase using antibody raised against the enzyme purified from rat liver supernatant (Sugimoto, H., and Yamashita, S. (1994) J. Biol. Chem. 269, 6252-6258). The 2,539-base pair cDNA encoded 564 amino acid residues with a calculated Mr of 60,794. The amino-terminal two-thirds of the deduced amino acid sequence significantly resembled Escherichia coli asparaginase I with the putative asparaginase catalytic triad Thr-Asp-Lys and was followed by leucine zipper motif. The carboxyl-terminal region carried ankyrin repeat. When the cDNA was transfected into HEK293 cells, not only lysophospholipase activity but also asparaginase and platelet-activating factor acetylhydrolase activities were expressed. Reverse transcription-polymerase chain reaction revealed that the transcript occurred at high levels in liver and kidney but was hardly detectable in lung and heart from which large form lysophospholipases had been purified, suggesting the presence of multiple forms of large form lysophospholipase in mammalian tissues.
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PMID:Cloning and expression of cDNA encoding rat liver 60-kDa lysophospholipase containing an asparaginase-like region and ankyrin repeat. 957 12


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