Disease relevance of CD248

• Human endosialin (tumor endothelial marker 1) is abundantly expressed in highly malignant and invasive brain tumors [1].
• After a median follow-up of 72.2 months it was found that patients who had recurrent disease and/or who had died from breast cancer had a significantly (P < 0.05) elevated level of TEM-1 compared to those patients who were disease free [2].
• RESULTS: TEM-1 (P = 0.01), TEM-7 (P = 0.04), TEM-7R (P = 0.03), TEM-8 (P = 0.001) significantly raised in colon cancer tissues compared with the levels detected in normal background tissues [3].
• Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin [4].
• 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 [5].

High impact information on CD248

• Clinically important ampicillin resistance in H. influenzae type b occurs by mechanisms other than by synthesis of TEM-1 beta-lactamase [6].
• Inhibition of nuclear migration or deletion of a Tem1p-like GTPase leads to a 'closed' mitosis, indicating that spindle pole bodies have to reach into the bud where MEN signalling participates in envelope removal [7].
• 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 [8].
• The structure of the 28 kDa beta-lactamase inhibitor protein-II (BLIP-II) in complex with the TEM-1 beta-lactamase has been determined to 2.3 A resolution [9].
• We have used the pH dependence of chemical modification of epsilon-amino groups by 2,4,6,-trinitrobenzenesulfonate and the pH dependence of the epsilon-methylene 1H and 13C chemical shifts (in enzyme selectively labeled with [epsilon-13C]lysine) to estimate the pKa of the relevant lysine residue, lysine-73, of TEM-1 beta-lactamase [10].

Chemical compound and disease context of CD248

• All isolates of Escherichia coli producing TEM 1, TEM 2 or OXA 1 beta-lactamases were sensitive to temocillin [11].
• Cefpodoxime was highly active against ampicillin-resistant enterobacteria producing the plasmid-mediated TEM-1, TEM-2 or OXA-1 enzymes, as was the case for the other newer compounds [12].
• The gene encoding TEM1 beta-lactamase was circularly permuted in a random fashion and subsequently randomly inserted into the gene encoding Escherichia coli maltose binding protein [13].
• beta-Lactamases with pIs of 5.4 and 8.1 were detected by hydrolysis of ampicillin and ceftriaxone respectively among cefotaxime resistant serovars of Salmonella spp. suggesting TEM-1 and an unidentified extended spectrum beta-lactamase have spread throughout these strains in Argentina [14].
• Furthermore it has high activity against Enterobacteriaceae, which contain classic TEM-1 beta-lactamases and those containing the new extended spectrum beta-lactamases, which hydrolyze parenteral third generation cephalosporins [15].

Biological context of CD248

• Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo [16].
• Here we describe the cDNA and genomic sequences for the mouse Tem1/endosialin homolog, the identification and characterization of its promoter region, and an extensive characterization of its expression pattern in murine and human tissues and murine cell lines in vitro [16].
• The sequence matches with an expressed sequence tag of unknown function in public data bases, named TEM1, which was independently linked to tumor endothelium by serial analysis of gene expression profiling [17].
• A restriction fragment of plasmid pBR322 bearing the TEM-1 beta-lactamase structural gene was electroeluted from agarose gels after digestion with EcoRI and HinfI [18].
• 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 [19].

Anatomical context of CD248

• Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium [20].
• Human tumor endothelial marker 1/endosialin (TEM1/endosialin) was recently identified as a novel tumor endothelial cell surface marker potentially involved in angiogenesis, although no specific function for this novel gene has been assigned so far [16].
• A Salmonella enterica serovar Typhimurium strain that harbored a plasmid carrying a TEM-1-type beta-lactamase gene was isolated from the blood and cerebrospinal fluid of an infant with meningitis [21].

Associations of CD248 with chemical compounds

• The cephacetrile-related compounds Ro 25-4095 and Ro 25-4835 were hydrolyzed by all three beta-lactamases with catalytic efficiencies (relative to penicillin G) ranging from approximately 5 (TEM-1, AmpC) to approximately 25 (TEM-3) [22].
• The in-vitro 50% inhibitory concentrations (IC50s) of latamoxef and imipenem against a set of plasmid-mediated beta-lactamases including TEM-1, TEM-3, TEM-5 and TEM-10 were determined by an enzymatic method using nitrocefin as substrate [23].
• 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 [24].
• Cefdinir appeared highly stable to the TEM-1 and SHV-1 beta-lactamases with only relatively minor degrees of hydrolysis being seen with TEM-3, -5 and -9 [25].
• Unlike cefamandole, cefoperazone, carbenicillin, and piperacillin, cefoxitin was not hydrolyzed by the common plasmid beta-lactamases, TEM-1, TEM-2, OXA-2, and SHV-1 [26].

Other interactions of CD248

• The expression of TEMs (TEM-1 to TEM-8) was assessed using RT-PCR and their transcript levels were determined using real-time-quantitative PCR (Q-RT-PCR) [3].
• 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) [27].
• GR69153 was stable to hydrolysis by the TEM-1 and TEM-5, SHV-1 and SHV-2, and K1 beta-lactamases, but some susceptibility to hydrolysis by the TEM-3, TEM-9, and P99 enzymes was observed [28].
• 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 [29].
• Seven clinical isolates belonging to four species and harbouring TEM-1, TEM-3 or TEM-6 were studied [30].

Analytical, diagnostic and therapeutic context of CD248

• beta-Lactamase identification by colony hybridization with 32P-labeled DNA probes for TEM-1, SHV-1, OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 was compared with isoelectric focusing in 122 clinical isolates making a variety of enzyme types [29].
• Documented ampicillin treatment failures of systemic Haemophilus influenzae type b infections have been associated with synthesis of a TEM-1 beta-lactamase [6].
• We have engineered the phage displayed TEM-1 beta-lactamase to generate enzymes that can be used in homogeneous immunoassays because their activity can be modulated by binding to monoclonal antibodies (Mabs) raised against an unrelated protein [31].
• Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography [32].
• The catalytic mechanism of beta-lactamases: NMR titration of an active-site lysine residue of the TEM-1 enzyme [10].

References