A role of Lys614 in the sulfotransferase activity of human heparan sulfate N‐deacetylase/N‐sulfotransferase

Sueyoshi, Tatsuya; Kakuta, Yoshimitsu; Pedersen, Lars C.; Wall, Frances E.; Pedersen, Lee G.; Negishi, Masahiko

doi:10.1016/s0014-5793(98)00913-2

Cited by 50 publications

(44 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Amino acid sequence alignment of the N -sulfotransferase domain of NDST-1 with the previously crystallized estrogen sulfotransferase revealed the structural motifs for the 5 -and 3 -phosphate binding of 3 -phosphoadenosine 5 -phosphosulfate (96), which contributed to the identification of these motifs in HS2ST, HS3ST, HS6ST, and many other GAG sulfotransferases. The crystal structure also identified possible catalytic residues (Lys 614 , Glu 642 , Lys 676 , and Lys 833 ) and an open cleft to accommodate an oligosaccharide acceptor (97).…”

Section: Three-dimensional Structures Of Ndst-1 and Glcat-imentioning

confidence: 90%

“…Currently the crystal structures for only two GAGsynthesizing enzymes NDST-1 (96,97) and GlcAT-I (37,98) have been solved at a resolution of 2.3Å. Amino acid sequence alignment of the N -sulfotransferase domain of NDST-1 with the previously crystallized estrogen sulfotransferase revealed the structural motifs for the 5 -and 3 -phosphate binding of 3 -phosphoadenosine 5 -phosphosulfate (96), which contributed to the identification of these motifs in HS2ST, HS3ST, HS6ST, and many other GAG sulfotransferases.…”

Section: Three-dimensional Structures Of Ndst-1 and Glcat-imentioning

confidence: 99%

See 1 more Smart Citation

Heparin and Heparan Sulfate Biosynthesis

2002

View full text Add to dashboard Cite

SummaryHeparan sulfate is one of the most informationally rich biopolymers in Nature. Its simple sugar backbone is variously modified to different degrees depending on the cellular conditions. Thus, it matures to have an enormously complicated structure, which most likely exhibits a considerable number of unique overlapping sequences with peculiar sulfation profiles. Such sequences are recognized by specific complementary proteins, which form a huge group of "heparin-binding proteins," and the sugar sequences in turn support unique functions of the respective proteins through specific interactions. The heparan sulfate sequences are not directly encoded by genes, but are created by elaborate biosynthetic mechanisms, which ensure the generation of these indispensable sequences. In heparan sulfate biosynthesis, the tetrasaccharide sequence (GlcAGal-Gal-Xyl-), designated the protein linkage region, is first assembled on a specific Ser residue at the glycosaminoglycan attachment site of a core protein. A heparan sulfate chain is then polymerized on this fragment by alternate additions of GlcNAc and GlcA through the actions of glycosyltransferases with overlapping specificities encoded by the tumor suppressor EXT family genes. Then follow various modifications by N-deacetylation and N-sulfation of glucosamine, C5-epimerization of GlcA and multiple O-sulfations of the component sugars. Recent studies have achieved purification of several, and molecular cloning of most, of the enzymes responsible for these reactions. Some of these enzymes are bifunctional. The availability of cDNA probes has facilitated elucidation of the crystal structures for two of the biosynthetic enzymes, demonstration of their intracellular location, and their occurrence in complexes to achieve rapid and efficient synthesis of complex sugar sequences. Genomic structure and transcript analysis have shown the existence of multiple isoforms for most of the sulfotransferases. Many aspects of the heparan sulfate biosynthetic scheme are shared by the structural analog heparin, which is synthesized in mast cells and some other mammalian cells and is several-fold higher degree of polymerization and more extensive modification than heparan sulfate.

show abstract

Section: Three-dimensional Structures Of Ndst-1 and Glcat-imentioning

confidence: 90%

Section: Three-dimensional Structures Of Ndst-1 and Glcat-imentioning

confidence: 99%

Heparin and Heparan Sulfate Biosynthesis

2002

View full text Add to dashboard Cite

show abstract

“…Subsequently, the X-ray crystal structures of three more cytosolic enzymes have been determined: human dopamine/catecholamine sulfotransferase (SULT1A3) (23,24), human hydroxysteroid sulfotransferase (hHST) (25), and human estrogen sulfotransferase (hEST) (26). By removing the amino-terminal membrane-binding region and the N-deacetylase domain from the Golgi membrane heparan sulfate N-deacetylase/N-sulfotransferase 1, only the N-sulfotransferase domain (NST1) was expressed in E. coli cells and cocrystallized with PAP (19,27). Similar to cytosolic mEST, hEST, SULT1A3, and hHST, the membrane NST1 structure is composed of a single ␣/␤ domain and displays the characteristic fivestranded parallel ␤-sheet (Fig.…”

Section: Overall Structurementioning

confidence: 99%

“…Homology alignments of the deduced amino acid sequences from these cDNAs identified various conserved residues (15,16). Also cDNA-based site-directed mutagenesis studies demonstrated that some of the residues, in fact, play critical roles in ST activity (17)(18)(19). Despite this progress, the opportunity to study STs based on the same structural features has only recently become possible with the solution of the first X-ray crystal structure of a ST (20).…”

mentioning

confidence: 99%

Structure and Function of Sulfotransferases

Negishi

Pedersen

Petrotchenko

et al. 2001

Archives of Biochemistry and Biophysics

Self Cite

311

231

View full text Add to dashboard Cite

Sulfotransferases (STs) catalyze the transfer reaction of the sulfate group from the ubiquitous donor 3 -phosphoadenosine 5 -phosphosulfate (PAPS) to an acceptor group of numerous substrates. This reaction, often referred to as sulfuryl transfer, sulfation, or sulfonation, is widely observed from bacteria to humans and plays a key role in various biological processes such as cell communication, growth and development, and defense. The cytosolic STs sulfate small molecules such as steroids, bioamines, and therapeutic drugs, while the Golgi-membrane counterparts sulfate large molecules including glucosaminylglycans and proteins. We have now solved the X-ray crystal structures of four cytosolic and one membrane ST. All five STs are globular proteins composed of a single ␣/␤ domain with the characteristic five-stranded ␤-sheet. The ␤-sheet constitutes the core of the Paps-binding and catalytic sites. Structural analysis of the PAPS-, PAP-, substrate-, and/or orthovanadate (VO 4 3؊ )-bound enzymes has also revealed the common molecular mechanism of the transfer reaction catalyzed by sulfotransferses. The X-ray crystal structures have opened a new era for the study of sulfotransferases.

show abstract

“…This coordination suggested that the lysine could be a catalytic residue participating in the dissociation of the sulfate group from PAPS. Site-directed mutagenesis studies have confirmed the functional importance of this residue in various sulfotransferase enzymes (5,(11)(12)(13). Accordingly, the transfer reaction has been proposed to proceed through an S N 2-like in-line displacement mechanism in which the conserved lysine and histidine play essential roles.…”

mentioning

confidence: 98%

Crystal Structure of the Human Estrogen Sulfotransferase-PAPS Complex

Pedersen¹,

Petrotchenko²,

Shevtsov

et al. 2002

Journal of Biological Chemistry

Self Cite

114

View full text Add to dashboard Cite

Estrogen sulfotransferase (EST) transfers the sulfate group from 3-phosphoadenosine 5-phosphosulfate (PAPS) to estrogenic steroids. Here we report the crystal structure of human EST (hEST) in the context of the V269E mutant-PAPS complex, which is the first structure containing the active sulfate donor for any sulfotransferase. Superimposing this structure with the crystal structure of hEST in complex with the donor product 3-phosphoadenosine 5-phosphate (PAP) and the acceptor substrate 17␤-estradiol, the ternary structure with the PAPS and estradiol molecule, is modeled.

show abstract

A role of Lys⁶¹⁴ in the sulfotransferase activity of human heparan sulfate N‐deacetylase/N‐sulfotransferase

Cited by 50 publications

References 25 publications

Heparin and Heparan Sulfate Biosynthesis

Heparin and Heparan Sulfate Biosynthesis

Structure and Function of Sulfotransferases

Crystal Structure of the Human Estrogen Sulfotransferase-PAPS Complex

Contact Info

Product

Resources

About