Disease relevance of SULT1A3

• Thermostable (SULT1A1) and thermolabile (SULT1A3) phenol sulfotransferases in human osteosarcoma and osteoblast cells [1].
• Generation and release of nitrotyrosine O-sulfate by HepG2 human hepatoma cells upon SIN-1 stimulation: identification of SULT1A3 as the enzyme responsible [2].
• The cDNA for the human monoamine-sulfating form of phenol sulfotransferase (hM-PST) was isolated from a T47D human breast carcinoma lambda gt10 cDNA library, and the active enzyme was expressed in Escherichia coli [3].
• Various human sulfotransferases (hP-PST, hM-PST, hHST) and rat sulfotransferases (rPST-IV, rHSTa) have already been expressed in Ames' Salmonella strains (in particular in TA1538) [4].
• The present study investigated STM and LTM for nonverbal material in three neurological conditions associated with memory impairment: bilateral medial temporal lobe lesions (patient H.M.), Parkinson's disease (PD) and Alzheimer's disease (AD) [5].

Psychiatry related information on SULT1A3

• The contrasting patterns of sparing and loss of STM and LTM in PD and global amnesia were present for both recognition and recall [5].
• The traditional concept of memory disorder is deficiency of the long-term (LTM) but not short-term (STM) component of memory [5].
• Ninety patients with a previous subarachnoid haemorrhage (SAH) were given a set of memory tests comprising immediate free recall of words (indexing long-term memory, LTM, and short-term memory, STM), final free recall of words (indexing LTM), final cued recall of words (indexing LTM), and a digit span test (indexing working memory, WM) [6].
• It is argued that the results are more consistent with psycholinguistic models than nonlinguistic models of STM, and implications for current STM models are discussed [7].

High impact information on SULT1A3

• Indexes of deamination, sulfoconjugation, and O-methylation, with the exception of a reduced deamination of dopamine and the activities of COMT, MAO-B, and TL-PST were not different in the two groups [8].
• Human SULT1A3 has been shown to be the major sulfotransferase that sulfonates dopamine [9].
• For SULT1A3, substrate inhibition is found for dopamine but not with pNP [9].
• We also propose, based on modeling and kinetic studies, that substrate inhibition by dopamine in SULT1A3 is caused by binding of two dopamine molecules in the active site [9].
• This activity is not present in the simple phenol-form PST, SULT1A1, which is otherwise >93% identical to SULT1A3 in amino acid sequence [10].

Chemical compound and disease context of SULT1A3

• Isolation of Salmonella enterica subspecies enterica serovar Paratyphi B dT+, or Salmonella Java, from Indonesia and alteration of the d-tartrate fermentation phenotype by disrupting the ORF STM 3356 [11].
• Trimeric Achromobacter cycloclastes Cu-containing nitrite reductase (CuNIR) proteins adsorbed on gold and graphite have been studied by ambient STM and in situ AFM [12].
• Some excellent results which might indicate clinically unknown effects of toluene such as hearing loss, impairments of time discrimination, and improvements of STM were also demonstrated [13].

Biological context of SULT1A3

• These experiments confirm the functional role of Glu146 in the selectivity of SULT1A3 for biogenic amines and suggest that this region is a key determinant of sulfotransferase substrate specificity [14].
• We used specific PCR-based assays and fluorescence in situ hybridization to verify that 2 SULT1A3 genes-SULT1A3 and SULT1A4-were present on chromosome 16 in all human DNA samples studied [15].
• However, following completion of the Human Genome Project, it appeared that SULT1A3 might be duplicated [15].
• Human SULT1A3 pharmacogenetics: gene duplication and functional genomic studies [15].
• Furthermore, reanalysis of previous gene resequencing data confirmed the presence of the SULT1A3 SNPs identified previously, but also revealed 11 novel polymorphisms, including 3 nonsynonymous cSNPs [15].

Anatomical context of SULT1A3

• Pharmacogenetic studies of TS and TL PST activities in the human blood platelet showed that the activities of these two isoforms were regulated by separate genetic polymorphisms [16].
• We recently cloned a cDNA for human liver TL PST and expressed it in COS-1 cells [17].
• DNA from NIGMS Human/Rodent Somatic Cell Hybrid Mapping Panels 1 and 2 was screened by use of the PCR, and the STM gene was mapped to chromosome 16 [17].
• As a first step toward cloning a cDNA for TL PST, the enzyme was purified from jejunal mucosa, the human tissue with the highest known specific activity, and purified TL PST was subjected to limited proteolysis and amino acid sequencing [18].
• The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3 [19].

Associations of SULT1A3 with chemical compounds

• Further studies using point-mutated SULT1A3s mutated at amino acid residues in these two regions and deletional mutants missing residues 84-86 and 84-90 implicate residue Glu-146 (in variable Region II of SULT1A3), as well as the presence of residues 84-90 of variable Region I, in the stereospecificity in the absence of Mn(2+) [10].
• Structure-function relationships in the stereospecific and manganese-dependent 3,4-dihydroxyphenylalanine/tyrosine-sulfating activity of human monoamine-form phenol sulfotransferase, SULT1A3 [10].
• T1AM, the most active thyronamine pharmacologically, was associated with the greatest SULT activity of the thyronamines tested in the liver pool and in both the expressed SULT1A3 and SULT1E1 preparations [20].
• Moreover, when estrone (which selectively inhibits expressed SULT1E1 and SULT1A3) was included in intestinal incubations, the high-affinity component of the Eadie-Hofstee plot for EE sulfation was inhibited, converting the plot from biphasic to monophasic [21].
• If the expression levels in tissues are additionally taken into account, SULT1A3 might be the predominant form for the sulphonation of ethanol in vivo, although a robust estimate requires further studies [22].

Physical interactions of SULT1A3

• Regions that are topologically equivalent to the disordered parts of SULT1A3 are involved in substrate and cofactor binding in estrogen and heparan sulfotransferase [23].

Enzymatic interactions of SULT1A3

• TS PST catalyzes the sulfate conjugation of micromolar concentrations of phenol and p-nitrophenol and TL PST catalyzes the sulfate conjugation of dopamine and other monoamines [24].

Regulatory relationships of SULT1A3

• The ability of hM-PST to sulfate a number of xenobiotics was examined and compared with the bacterially expressed human phenol-sulfating form of PST (hP-PST) [3].

Other interactions of SULT1A3

• The change of a single amino acid, E146A, was sufficient to transform the catalytic properties and substrate preference of SULT1A3, such that they closely resembled those of SULT1A1 [14].
• In humans, catecholamines such as dopamine are extensively sulfated, and a SULT isoform (SULT1A3 or the monoamine-sulfating form of phenolsulfotransferase) has evolved with considerable selectivity for dopamine and other biogenic amines [14].
• The remaining enzymes studied (SULT1A3, 1C1, 1E1, 2A1, 2B1a, 2B1b, 4A1 and NAT1) did not indicate any activation of N-OH-MeAalphaC [25].
• From these data, we conclude that human liver TS-PST but not TL-PST or DHEA-ST can metabolically activate the proximate human carcinogen N-OH-ABP to a reactive sulfuric acid ester intermediate that binds covalently to DNA [26].
• We previously cloned and expressed a cDNA for human liver TL PST and localized its gene, STM, to human chromosome 16p11.2, a region of the chromosome to which the Batten disease gene is also localized [27].

Analytical, diagnostic and therapeutic context of SULT1A3

• Human thermolabile phenol sulfotransferase gene (STM): molecular cloning and structural characterization [27].
• We also investigated further the role of Glu(146) in SULT1A3 using site-directed mutagenesis and showed that it plays a key role not only in defining selectivity for dopamine but also in preventing many phenolic xenobiotics from binding to the enzyme [28].
• Western blot analysis of mammary cytosolic protein showed detectable levels of SULT1A1 and SULT1A3 [29].
• The developmental expression of SULT1A3 and SULT1A1 in liver and brain was confirmed by immunoblot, and immunohistochemistry of developing liver showed substantial expression of these proteins in hemopoietic cells in fetal liver [30].
• High-performance liquid chromatography (HPLC) of the reaction products confirmed the known products of SULT1A1 and SULT1A3 [1].

References