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

Here the structure of human glyoxalase II has been investigated by studying unfolding at equilibrium and refolding. Human glyoxalase II contains two tryptophan residues situated at the N-terminal (Trp57) and C-terminal (Trp199) regions of the molecule. Trp57 is a non-conserved residue located within a "zinc binding motif" (T/SHXHX57DH) which is strictly conserved in all known glyoxalase II sequences as well as in metal-dependent beta-lactamase and arylsulfatase. Site-directed mutagenesis has been used to construct single-tryptophan mutants in order to characterize better the guanidine-induced unfolding intermediates. The denaturation at equilibrium of wild-type glyoxalase II, as followed by activity, intrinsic fluorescence and CD, is multiphasic, suggesting that different regions of varying structural stability characterize the native structure of glyoxalase II. At intermediate denaturant concentration (1.2 M guanidine) a molten globule state is attained. The reactivation of the denatured wild-type enzyme occurs only in the presence of Zn(II) ions. The results show that Zn(II) is essential for the maintenance of the native structure of glyoxalase II and that its binding to the apoenzyme occurs during an essential step of refolding. The comparison of unfolding fluorescence transitions of single-trypthophan mutants with that of wild-type enzyme indicates that the strictly conserved "zinc binding motif" is located in a flexible region of the active site in which Zn(II) participates in catalysis.
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PMID:Unfolding and refolding of human glyoxalase II and its single-tryptophan mutants. 1043 33

Recently, the zinc metallo-hydrolase family of the beta-lactamase fold has grown quite rapidly, accompanied by the accumulation of sequence and structure data. The variety of the biological functions of the family is higher than expected. In addition, the members often have mosaic structures with additional domains. The family includes class B beta-lactamase, glyoxalase II, arylsulfatase, flavoprotein, cyclase/dehydrase, an mRNA 3'-processing protein, a DNA cross-link repair enzyme, a DNA uptake-related protein, an alkylphosphonate uptake-related protein, CMP-N-acetylneuraminate hydroxylase, the romA gene product, alkylsulfatase, and insecticide hydrolases. In this minireview, the functional and structural varieties of the growing protein family are described.
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PMID:Expansion of the zinc metallo-hydrolase family of the beta-lactamase fold. 1151 44

ElaC is a widespread gene found in eubacteria, archaebacteria, and mammals with a highly conserved sequence. Two human ElaC variants were recently associated with cancer (Tavtigian, S. V., Simard, J., Teng, D. H., Abtin, V., Baumgard, M., Beck, A., Camp, N. J., Carillo, A. R., Chen, Y., Dayananth, P., Desrochers, M., Dumont, M., Farnham, J. M., Frank, D., Frye, C., Ghaffari, S., Gupte, J. S., Hu, R., Iliev, D., Janecki, T., Kort, E. N., Laity, K. E., Leavitt, A., Leblanc, G., McArthur-Morrison, J., Pederson, A., Penn, B., Peterson, K. T., Reid, J. E., Richards, S., Schroeder, M., Smith, R., Snyder, S. C., Swedlund, B., Swensen, J., Thomas, A., Tranchant, M., Woodland, A. M., Labrie, F., Skolnick, M. H., Neuhausen, S., Rommens, J., and Cannon-Albright, L. A. (2001) Nat. Genet. 27, 172-180; Yanaihara, N., Kohno, T., Takakura, S., Takei, K., Otsuka, A., Sunaga, N., Takahashi, M., Yamazaki, M., Tashiro, H., Fukuzumi, Y., Fujimori, Y., Hagiwara, K., Tanaka, T., and Yokota, J. (2001) Genomics 72, 169-179). Analysis of the primary sequence indicates homology to an arylsulfatase and predicts a metallo-beta-lactamase fold. At present, no ElaC gene product has been investigated. We cloned the Escherichia coli ElaC gene and purified the recombinant gene product. An enzymatic analysis showed that ElaC does not encode an arylsulfatase but rather encodes a phosphodiesterase that hydrolyzes bis(p-nitrophenyl)phosphate with a k(cat) of 59 s(-1) and K' of 4 mm. Kinetic analysis of the dimeric enzyme revealed positive cooperativity for the substrate bis(p-nitrophenyl)phosphate with a Hill coefficient of 1.6, whereas hydrolysis of the substrate thymidine-5'-p-nitrophenyl phosphate followed Michaelis-Menten kinetics. Furthermore, the enzyme is capable of binding two zinc or two iron ions. However, it displays phosphodiesterase activity only in the zinc form. The metal environment characterized by zinc K-edge x-ray absorption spectroscopy was modeled with two histidine residues, one carboxylate group, and 1.5 oxygen atoms. This corresponds to the coordination found in other metallo-beta-lactamase domain proteins. Phosphodiesterase activity is strongly dependent on the presence of zinc. These results identify the currently unassigned gene product ElaC to be a novel binuclear zinc phosphodiesterase.
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PMID:ElaC encodes a novel binuclear zinc phosphodiesterase. 1202 81

In an effort to determine the physiological role of Arabidopsis thaliana Glx2-1, we attempted to uncover a substrate for the enzyme. Glx2-1 did not effectively process 192 diverse substrates found in a commercial screen used for microorganism identification or exhibit arylsulfatase, lactonase, or phosphotriesterase activities. However, Glx2-1 does exhibit beta-lactamase activity with k(cat)/KM values from 10(3) to 10(5) M(-1) s(-1). Glx2-1 can hydrolyze cephalosporins and carbapenems, albeit with rate constants slower than those of most metallo-beta-lactamases. The potential role of a beta-lactamase in the mitochondria of plant cells is briefly discussed.
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PMID:Arabidopsis thaliana mitochondrial glyoxalase 2-1 exhibits beta-lactamase activity. 1973 13