Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.5 (urease)
 7,257 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent determination of the three-dimensional structure of urease revealed striking similarities of enzyme architecture to adenosine deaminase and phosphotriesterase, evidence of a distant evolutionary relationship that had gone undetected by one-dimensional sequence comparisons. Here, based on an analysis of conservation patterns in three dimensions, we report the discovery of the same active-site architecture in an even larger set of enzymes involved primarily in nucleotide metabolism. As a consequence, we predict the three-dimensional fold and details of the active site architecture for dihydroorotases, allantoinases, hydantoinases, AMP-, adenine and cytosine deaminases, imidazolonepropionase, aryldialkylphosphatase, chlorohydrolases, formylmethanofuran dehydrogenases, and proteins involved in animal neuronal development. Two member families are common to archaea, eubacteria, and eukaryota. Thirteen other functions supported by the same structural motif and conserved chemical mechanism apparently represent later adaptations for different substrate specificities in different cellular contexts.
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PMID:An evolutionary treasure: unification of a broad set of amidohydrolases related to urease. 914 92

Cryptococcus gattii is a primary pathogenic yeast, increasingly important in public health, but factors responsible for its host predilection and geographical distribution remain largely unknown. We have characterized C. gattii STE12alpha to probe its role in biology and pathogenesis because this transcription factor has been linked to virulence in many human and plant pathogenic fungi. A full-length STE12alpha gene was cloned by colony hybridization and sequenced using primer walk and 3' rapid amplification of cDNA ends strategies, and a ste12alpha delta gene knockout mutant was created by URA5 insertion at the homologous site. A semiquantitative analysis revealed delayed and poor mating in ste12alpha delta mutant; this defect was not reversed by exogenous cyclic AMP. C. gattii parent and mutant strains showed robust haploid fruiting. Among putative virulence factors tested, the laccase transcript and enzymatic activity were down regulated in the ste12alpha delta mutant, with diminished production of melanin. However, capsule, superoxide dismutase, phospholipase, and urease were unaffected. Similarly, Ste12 deficiency did not cause any auxotrophy, assimilation defects, or sensitivity to a large panel of chemicals and antifungals. The ste12alpha delta mutant was markedly attenuated in virulence in both BALB/c and A/Jcr mice models of meningoencephalitis, and it also exhibited significant in vivo growth reduction and was highly susceptible to in vitro killing by human neutrophils (polymorphonuclear leukocytes). In tests designed to simulate the C. gattii natural habitat, the ste12alpha delta mutant was poorly pigmented on wood agar prepared from two tree species and showed poor survival and multiplication in wood blocks. Thus, STE12alpha plays distinct roles in C. gattii morphogenesis, virulence, and ecological fitness.
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PMID:Transcription factor STE12alpha has distinct roles in morphogenesis, virulence, and ecological fitness of the primary pathogenic yeast Cryptococcus gattii. 1683 51

Ureases (EC 3.5.1.5) are highly homologous enzymes found in plants, bacteria and fungi. Canatoxin, an isoform Canavalia ensiformis urease, has several biological properties unrelated to its ureolytic activity, like platelet-aggregating and pro-inflammatory effects. Here, we describe that Bacillus pasteurii urease (BPU) also induces aggregation of rabbit platelets, similar to the canatoxin-induced effect (ED(50) 0.4 and 0.015 mg/mL, respectively). BPU induced-aggregation was blocked in platelets pretreated with dexamethasone and esculetin, a phospholipase A(2) and a lipoxygenase inhibitor, respectively, while platelets treated with indomethacin, a cyclooxygenase inhibitor, showed increased response to BPU. Methoxyverapamil (Ca(2+) channel blocker) and AMP (ADP antagonist) abrogated urease-induced aggregation, whereas the PAF-acether antagonist Web2170 had no effect. We concluded that platelet aggregation induced by BPU is mediated by lipoxygenase-derived eicosanoids and secretion of ADP from the platelets through a calcium-dependent mechanism. Potential relevance of these findings for bacterium-plant interactions and pathogenesis of bacterial infections are discussed.
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PMID:Bacillus pasteurii urease shares with plant ureases the ability to induce aggregation of blood platelets. 1683 15