Sulfation of all macromolecules in higher organisms requires the high-energy donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS). PAPS is synthesized via the sequential actions of two cytoplasmic enzymes, ATP sulfurylase and APS kinase, and then must be transferred across the Golgi membrane for utilization by lumenal sulfotransferases. Following the kinetic characterization of the PAPS translocase as a specific transporter that act through an antiport mechanism with PAP as the returning ligand [Ozeran, J.D., Westley, J., Schwartz, N.B. (1996) Biochemistry 35, 3685-3694 (accompanying paper)], the present study describes the identification and physical characterization of the PAPS translocase from rat liver Golgi membranes. The following evidence suggests the PAPS translocase is a membrane spanning protein of approximately 230 kDa: isolation by affinity chromatography on beta-methylene PAPS matrices of a 230 kDa Golgi membrane protein concomitant with PAPS translocase activity; demonstration that the 230 kDa protein possesses the only PAPS binding site accessible to the cytoplasmic face of intact Golgi membranes, while several other PAPS binding proteins are labeled in solubilized membrane preparations; reduction in size of the 230 kDa membrane protein and loss of PAPS translocase activity following protease treatment; estimation via hydrodynamic analysis of a molecular size of the membrane protein associated with PAPS translocase activity; and correlation of beta-methylene PAPS binding and labeling of the 230 kDa Golgi protein with PAPS translocase activity in artificial liposomes. These and the accompanying data have permitted the identification of the first of a potentially large class of Golgi membrane nucleotide-metabolite transporters.
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http://dx.doi.org/10.1021/bi951303m | DOI Listing |
Nat Chem Biol
October 2013
Pharmaceutical Institute, University of Tübingen, Tübingen, Germany.
Caprazamycins (CPZs) belong to a group of liponucleoside antibiotics inhibiting the bacterial MraY translocase, an essential enzyme involved in peptidoglycan biosynthesis. We have recently identified analogs that are decorated with a sulfate group at the 2″-hydroxy of the aminoribosyl moiety, and we now report an unprecedented two-step sulfation mechanism during the biosynthesis of CPZs. A type III polyketide synthase (PKS) known as Cpz6 is used in the biosynthesis of a group of new triketide pyrones that are subsequently sulfated by an unusual 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfotransferase (Cpz8) to yield phenolic sulfate esters, which serve as sulfate donors for a PAPS-independent arylsulfate sulfotransferase (Cpz4) to generate sulfated CPZs.
View Article and Find Full Text PDFChem Biol Interact
February 1998
Department of Pediatrics, University of Chicago Hospitals, IL 60637, USA.
Extensive studies on the mammalian sulfate-activating enzymes and PAPS translocase have enhanced our understanding of the overall pathway of sulfate activation and utilization. Isolation of the PAPS-synthesizing activities from rat chondrosarcoma and preparation of stable non-hydrolyzable analogs of APS and PAPS have facilitated the kinetic characterization of mammalian ATP sulfurylase and APS kinase. These studies provided the basis for further experimental work showing that APS, the labile intermediate product, is channeled directly between the sulfurylase and kinase active sites.
View Article and Find Full Text PDFBiochemistry
March 1996
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
Sulfation of all macromolecules in higher organisms requires the high-energy donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS). PAPS is synthesized via the sequential actions of two cytoplasmic enzymes, ATP sulfurylase and APS kinase, and then must be transferred across the Golgi membrane for utilization by lumenal sulfotransferases. Following the kinetic characterization of the PAPS translocase as a specific transporter that act through an antiport mechanism with PAP as the returning ligand [Ozeran, J.
View Article and Find Full Text PDFBiochemistry
March 1996
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
In order to gain an understanding of the mechanisms involved in the transfer of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) from the cytosol where it is synthesized to the Golgi lumen where it serves as the universal sulfate donor for sulfate ester formation in higher organisms, we have undertaken a kinetic characterization of the PAPS translocase from rat liver Golgi. Analyzing the PAS translocase activity in both intact Golgi vesicles and in a reconstituted liposome system, we have determined a number of physical and kinetic parameters. Strong competitive inhibition in zero-trans uptake experiments only with beta-methylene PAPS and adenosine 3',5'-biphosphate (PAP) suggest the transporter is highly specific for the 3'-phosphate.
View Article and Find Full Text PDFAnal Biochem
October 1991
Department of Pediatrics, Joseph P. Kennedy Jr. Mental Retardation Research Center, University of Chicago, Illinois 60637.
3'-Phosphoadenosine 5'-phosphosulfate (PAPS) functions as the high-energy sulfate donor for sulfate ester synthesis in all higher organisms. This activated sulfate, like its adenosine 5'-phosphosulfate precursor, is both chemically labile and vulnerable to sulfohydrolase degradation. These obstacles have limited the utility of the native PAPS in the purification and mechanistic description of the numerous PAPS-utilizing enzymes.
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