Disease relevance of RASD2

• All isolates of Escherichia coli producing TEM 1, TEM 2 or OXA 1 beta-lactamases were sensitive to temocillin [1].
• A new natural TEM-2 derivative, named TEM-72, was identified in a Proteus mirabilis strain and in a Morganella morganii strain isolated in Italy in 1999 [2].
• While the number of characterised beta-lactamases may exceed 100, only a few are a problem in the treatment of community-acquired infections (TEM-1, TEM-2, SHV-1, BRO-1) [3].
• Foramidocillin was not hydrolyzed by the common plasmid-mediated beta-lactamases TEM-1, TEM-2, OXA-2, PSE-4, and SHV-1, by the chromosomal beta-lactamases P99 of Enterobacter cloacae and K1 of Klebsiella oxytoca, or by the Sabath-Abraham enzyme of P. aeruginosa [4].
• FK482 was not hydrolyzed by the TEM-1 and TEM-2 beta-lactamases but was hydrolyzed by TEM-3 and the Proteus vulgaris enzyme [5].

High impact information on RASD2

• Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these beta-lactamases [6].
• We show that in PC12 cells, Rhes is targeted to the plasma membrane by farnesylation [7].
• However, Rhes is not transforming in murine fibroblasts [7].
• The cyclic acyl phosph(on)ates, 1-hydroxy-5-phenyl-2,6-dioxaphosphorinone(3)-1-oxide, its 4-phenyl isomer, and the phosphonate (2-oxo) analogue of the latter inhibited typical class A (TEM-2) and class C (Enterobacter cloacae P99) beta-lactamases in a time-dependent fashion [8].
• The amino acid sequence deduced from the corresponding bla gene showed two amino acid replacements with respect to the TEM-2 sequence: Glu-104 to Lys and His-153 to Arg [9].

Chemical compound and disease context of RASD2

• The effectiveness of clavulanic acid, sulbactam, quinacillin sulfone, and the carbapenems MM13902 and MM4550 as inhibitors of TEM-2 beta-lactamase in growing cultures of gram-negative bacteria has been studied [10].
• The mutant 554 of TEM-2 beta-lactamase was selected for a decrease in the resistance to carbenicillin of an Escherichia coli K12 carrier [11].

Biological context of RASD2

• The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes [12].
• Recently, reports from several countries have pointed to the clinical relevance of 'extended-spectrum enzymes' derived by point mutation from the 'classical' TEM-1 or TEM-2 enzymes [13].
• Resistance phenotypes were consistent with overproduction of TEM-1, TEM-2 or SHV-1 beta-lactamases in 56 strains, with AmpC cephalosporinase hyperproduction in 46 strains, and with production of inhibitor-resistant penicillinases in 49 strains [14].
• The probe hybridized only with TEM-2 and OXA-2 class plasmids [15].
• ME1228 was not hydrolyzed by TEM-1, TEM-2, SHV-1, and S. aureus plasmid beta-lactamases and was stable against hydrolysis by Richmond-Sykes type 1a, 1c, 1d, and IV chromosomal beta-lactamases [16].

Anatomical context of RASD2

• Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell [17].

Associations of RASD2 with chemical compounds

• Rhes/RASD2 is a novel Ras homolog with almost restricted expression in the brain and highly enriched in the striatum, where it is controlled by thyroid hormone during the postnatal period [18].
• Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability [12].
• Rhes is shown to be expressed in beta-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective [17].
• It was concluded that resistance to aztreonam and cefuroxime in these isolates was conferred by a beta-lactamase distinct from TEM-1, TEM-2 and SHV-1, but possibly derived from TEM-like enzymes [19].
• All the enzymes were inhibited well by clavulanic acid, with I50 values ranging from 4.3 to 12 nM, compared to 130 nM for TEM-2 [20].

Regulatory relationships of RASD2

• Little is known about its biochemical properties and cell signaling function, but the data available so far indicate that Rhes is constitutively bound to GTP and activates PI3K, and, on the other hand, interferes with cAMP/PKA pathway activation induced by G protein-coupled receptors [18].

Other interactions of RASD2

• The expressions of TEM-2 and TEM-6 were found to be not significantly different between tumor tissues and normal tissues (P > 0.05) [21].
• A TEM-2 derivative, TEM-201, with characteristics similar to those of TEM-7 was selected spontaneously in the presence of ceftazidime in vitro [22].
• Cross-hybridization was observed between TEM-1 and TEM-2 or TLE-1, between SHV-1 and SHV-2, between OXA-1 and OXA-4, between OXA-2 and OXA-3 (weak), between PSE-2 and OXA-6 or OXA-5 (weak), and among PSE-1, PSE-4, and CARB-3 [23].

References