Disease relevance of speB

• The speB gene of Escherichia coli encodes agmatine ureohydrolase (AUH), a putrescine biosynthetic enzyme [1].
• In the extreme thermophile Thermus thermophilus, a disruption mutant of a gene homologous to speB (coding for agmatinase = agmatine ureohydrolase) accumulated N1-aminopropylagmatine (N8-amidino-1,8-diamino-4-azaoctane, N8-amidinospermidine), a new compound, whereas all other polyamines produced by the wild-type strain were absent from the cells [2].
• Human mitochondrial agmatinase shows a considerable level of sequence similarity to bacterial agmatinases, including a putative agmatinase from Deinococcus radiodurans [3].

High impact information on speB

• To confirm our speculation, we purified the expression product of the speB homolog and confirmed that the enzyme hydrolyzes N1-aminopropylagmatine to spermidine but does not act on agmatine [2].
• The speB gene is transcribed either from its own promoter or as a polycistronic message from the promoter of the speA gene encoding arginine decarboxylase [1].
• Two open reading frames (ORF1 and ORF2) are present on the strand complementary to speB; approximately 90% of ORF2 overlaps the speB coding region [1].
• Influence of cyclic AMP, agmatine, and a novel protein encoded by a flanking gene on speB (agmatine ureohydrolase) in Escherichia coli [1].
• Deletion of ORF1 from a plasmid containing ORF1, ORF2, and speB reduced the activity of AUH by 83% [1].

Chemical compound and disease context of speB

• Manganese is essential for catalytic activity of Escherichia coli agmatinase [4].
• The putative agmatinase from D. radiodurans has been overexpressed in Escherichia coli and crystallized at 297 K using polyethylene glycol 3000 as a precipitant [3].
• Arginine decarboxylase (ADC) and agmatinase are part of an operon in Escherichia coli, which constitutes the primary pathway of polyamine synthesis from arginine [5].

Biological context of speB

• This sequence contained the speA open reading frame (ORF) as well as partial speB and metK ORFs [6].
• The enzyme agmatinase catalyses the hydrolysis of agmatine to putresine and urea [3].
• We describe here the cloning of the agmatinase gene and the tissue distribution of its transcription product [5].
• Three-dimensional models, generated by homology modelling techniques, indicated that the side chains of Asp153 and Asn153 can perfectly fit in essentially the same position in the active site of E. coli agmatinase [7].

Associations of speB with chemical compounds

• Consequently, agmatine affects selection between the monocistronic and the polycistronic modes of speB transcription [1].
• In contrast, cyclic AMP (cAMP) repressed AUH activity of chromosomally encoded AUH but had no effect on plasmid-borne speB nor phi(speB-phoA) [1].

Analytical, diagnostic and therapeutic context of speB

• Crystallization and preliminary X-ray crystallographic analysis of a putative agmatinase from Deinococcus radiodurans [3].
• Insights into the reaction mechanism of Escherichia coli agmatinase by site-directed mutagenesis and molecular modelling [7].

References