Disease relevance of ENOPH1

• A new method for detecting circulating tumor cells that is based on magnetic-activated cell separation (MACS) and nested mutant allele-specific amplification (nested MASA) was evaluated in patients with colorectal cancer using the p53 and K-ras genes as genetic markers [1].
• From these data it appears that urinary MASA may be used to diagnose bacterial prostatitis in situations in which quantitative bacteriologic cultures cannot be performed [2].
• The effect of nixtamalization, the process by which masa flour is produced by alkaline hydrolysis of corn, on the organ-specific toxicity of F. moniliforme culture material containing fumonisin B1 (FB1) was studied and the effectiveness of nixtamalization and water extraction for detoxifying culture material was compared [3].

High impact information on ENOPH1

• The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex [4].
• We identify UBE1L as the E1 enzyme that catalyzes the first activation step in the conjugation of ISG15, and show that the NS1B protein inhibits this activation step in vitro [5].
• Expression of HPV16 E7 in a cell line with a temperature-sensitive mutation in the E1 enzyme of the ubiquitin pathway demonstrated that degradation of Rb was ubiquitin dependent [6].
• One such residue, Ala-72 (Arg in ubiquitin), is shown to perform a key role in selecting against reaction with the ubiquitin E1 enzyme, thereby acting to prevent the inappropriate diversion of NEDD8 into ubiquitin-specific pathways [7].
• We also succeeded in isolating inhibitors against the proteasome and E1 enzyme from marine natural resources [8].

Biological context of ENOPH1

• This rescue confirms that the phenotype observed in the ts20 cells is due to a defect in the E1 enzyme [9].
• A temperature-sensitive growth mutant tsFS20 isolated from mouse FM3A cells was identified as a mutant with thermolabile ubiquitin-activating enzyme E1 by transfection with a full-length cDNA encoding the human E1 enzyme and cell-cell hybridization with an authentic E1 mutant ts85 previously isolated from FM3A cells [10].

Associations of ENOPH1 with chemical compounds

• Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine salvage pathway that catalyzes the continuous reactions of 2,3-diketo-5-methylthio-1-phosphopentane to yield the aci-reductone metabolite using Mg2+ as cofactor [11].
• The results suggested the some amino acid other than aspartate or glutamate, possibly a cysteine residue, located on a large tryptic peptide of the E1 enzyme, may have reacted with DCC [12].

Physical interactions of ENOPH1

• Crystal structure of human E1 enzyme and its complex with a substrate analog reveals the mechanism of its phosphatase/enolase activity [11].

Other interactions of ENOPH1

• Although the E1 enzyme for ISG15 (Ube1L/E1(ISG15)) has been identified, the identities of the downstream components of the ISG15 conjugation cascade have remained elusive [13].
• AIMS/METHODS: Using purified E1 component of pyruvate dehydrogenase complex (PDC) from bovine heart, we measured the levels of anti-E1 antibodies in PBC sera using ELISA and determined the degree of inhibition that these antibodies exerted on E1 enzyme activity [14].

Analytical, diagnostic and therapeutic context of ENOPH1

• A rapid and simple enzyme-linked immunosorbant assay (ELISA) was developed to measure urinary total immunoglobulins and antibodies to common gram negative organisms (mixed antigen-specific antibodies, MASA) [2].
• During ubiquitin ligation, an E2 conjugating enzyme receives ubiquitin from an E1 enzyme and then interacts with an E3 ligase to modify substrates [15].

References