Sulfotransferasen: Struktur, Mechanismus, biologische Aktivität, Inhibierung, Anwendung in Synthesen

Abstract

Seit langem ist bekannt, dass die Sulfonierung von Biomolekülen in einer Vielzahl von Organismen stattfindet, von Prokaryoten bis hin zu vielzelligen Spezies, und ständig werden neue biologische Funktionen entdeckt, die mit dieser Umsetzung verknüpft sind. Frühe Studien zu Sulfotransferasen (STs), den Enzymen, die Sulfonierungen katalysieren, konzentrierten sich primär auf zytosolische STs, die an Entgiftungsreaktionen, der Hormonregulation und am Wirkstoffmetabolismus beteiligt sind. Obwohl man von ihrer Existenz gewusst hat, wurden membranassoziierte STs bis vor kurzem kaum untersucht. Sie sind an der Sulfonierung komplexer Kohlenhydrate und Proteine beteiligt und spielen eine zentrale Rolle bei einer Reihe von molekularen Erkennungsmechanismen und biochemischen Signalwegen. Des Weiteren hängen STs mit vielen pathophysiologischen Prozessen zusammen. Dies führte zu einem verstärkten Interesse an den komplexen Funktionen von STs und an der Möglichkeit zur Targetierung in therapeutischen Eingriffen. In diesem Aufsatz werden die Fortschritte bei der Aufklärung der Strukturen und Mechanismen von Sulfotransferasen sowie ihre biologische Aktivität, Inhibierung und Anwendung in der Synthese diskutiert.

Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications

“…[66] PAPS is the biological reagent for transfer of activated sulfuryl (SO 3 À ) groups to nucleophiles in both small molecules (e.g. The SO 3 À group is also transferred from phosphoadenosine phosphosulfate (PAPS) to tyrosine side chains in proteins.…”

The Biosynthesis of Liposidomycin‐like A‐90289 Antibiotics Featuring a New Type of Sulfotransferase

“…Sulfate incorporation in mammals is a key step in detoxification of aromatic hydrocarbons and for molecular recognition and signaling. [8] Enzymes that catalyze this event have hitherto been identified as PAPS-dependent sulfotransferases and are represented by estrogen and heparin sulfotransferases. [8] In bacteria, sulfate transfer enzymes are also known, but these enzymes, which form a distinct class of enzymes named aryl sulfotransferases, utilize a PAPS-independent mechanism that employ an aryl sulfate donor substrate and phenolic-type acceptor substrate.…”

“…[8] Enzymes that catalyze this event have hitherto been identified as PAPS-dependent sulfotransferases and are represented by estrogen and heparin sulfotransferases. [8] In bacteria, sulfate transfer enzymes are also known, but these enzymes, which form a distinct class of enzymes named aryl sulfotransferases, utilize a PAPS-independent mechanism that employ an aryl sulfate donor substrate and phenolic-type acceptor substrate. [13][14][15][16] LipB has closest sequence homology to the latter class of enzymes, and we have demonstrated here that p-nitrophenylsulfate does serve as the sulfate donor as expected from sequence analysis.…”

“…SANK 60405 to allow a complete comparison of clusters and, importantly, to identify the mechanism of sulfate incorporation, which remains poorly explored for bacteria. [8] Thus, the whole genome was sequenced by using 454 technology, and complete analysis of the resulting 1199 contiguous sequences encompassing 7.9 MB of unique DNA sequence revealed one contiguous sequence containing three tandem O-methyltransferases and several orfs encoding proteins of expected function. A close comparison of this contiguous sequence and the caprazamycin gene cluster revealed a nearly identical genetic architecture with homologous proteins having 70-92 % sequence identity, and we therefore annotated orfs in this contiguous sequence as lipA, lipB, etc., for liposidomycin-type biosynthetic gene cluster (Figure 1).…”

A Hyaluronidase Supercatalyst for the Enzymatic Polymerization to Synthesize Glycosaminoglycans

“…[44] Biosynthesis of Ch is performed in the Golgi apparatus by the catalysis of chondroitin synthase (EC 2.4.1.-) and other glycosyltransferases with UDP-N-acetyl-d-galactosamine (UDP-GalNAc) and UDP-GlcA as substrates, [34,[45][46][47][48] followed by selective sulfation by several kinds of specific sulfotransferases. [7,49] Thus HA, Ch, and ChS play crucial roles in living systems; structurally well-defined samples are essential to elucidate their molecular functions for vital activities in living system. Their chemical or biochemical synthesis is challenging, [50] and a facile and efficient method to prepare these biomacromolecules with complicated structures has been an important unsolved problem.…”