Sulfotransferase
| Sulfotransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal Structure of Human Sulfotransferase SULT1A3 in Complex with Dopamine and 3-Phosphoadenosine 5-Phosphate | |||||||||
| Identifiers | |||||||||
| EC no. | 2.8.2.- | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
In biochemistry, sulfotransferases (SULTs) are transferase enzymes that catalyze the transfer of a sulfo group (R−SO−3) from a donor molecule to an acceptor alcohol (R−OH) or amine (R−NH2).[1] The most common sulfo group donor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In the case of alcohol as acceptor, the product is a sulfate (R−OSO−3):
![{\displaystyle {\mathrm {R} {-}\mathrm {SO} {\vphantom {A}}_{\smash[{t}]{3}}{\vphantom {A}}^{-}}\ +\ {\mathrm {R} {\vphantom {A}}^{\prime }{-}\mathrm {OH} }\quad {\xrightarrow[{\text{ SULT }}]{}}\quad {\mathrm {R} {-}\mathrm {H} }\ +\ {\mathrm {R} {\vphantom {A}}^{\prime }{-}\mathrm {OSO} {\vphantom {A}}_{\smash[{t}]{3}}{\vphantom {A}}^{-}}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/309f6adbd894014d72d03faf7b24c04b81e1f235)
whereas an amine leads to a sulfamate (R−NH−SO−3):
![{\displaystyle {\mathrm {R} {-}\mathrm {SO} {\vphantom {A}}_{\smash[{t}]{3}}{\vphantom {A}}^{-}}\ +\ {\mathrm {R} {\vphantom {A}}^{\prime }{-}\mathrm {NH} {\vphantom {A}}_{\smash[{t}]{2}}}\quad {\xrightarrow[{\text{ SULT }}]{}}\quad {\mathrm {R} {-}\mathrm {H} }\ +\ {\mathrm {R} {\vphantom {A}}^{\prime }{-}\mathrm {NHSO} {\vphantom {A}}_{\smash[{t}]{3}}{\vphantom {A}}^{-}}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/b5606063c04db8ea36fe2dd0674ec64f45c93be9)
Both reactive groups for a sulfonation via sulfotransferases may be part of a protein, lipid, carbohydrate or steroid.[2]
Examples
[edit]The following are examples of sulfotransferases:
- carbohydrate sulfotransferase: CHST1, CHST2, CHST3, CHST4, CHST5, CHST6, CHST7, CHST8, CHST9, CHST10, CHST11, CHST12, CHST13, CHST14
- galactose-3-O-sulfotransferase: GAL3ST1, GAL3ST2, GAL3ST3, GAL3ST4
- heparan sulfate 2-O-sulfotransferase: HS2ST1
- heparan sulfate 3-O-sulfotransferase: HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3ST6
- heparan sulfate 6-O-sulfotransferase: HS6ST1, HS6ST2, HS6ST3
- N-deacetylase/N-sulfotransferase: NDST1, NDST2, NDST3, NDST4
- tyrosylprotein sulfotransferase: TPST1, TPST2
- uronyl-2-sulfotransferase
- Estrone sulfotransferase
- Chondroitin 4-sulfotransferase
- other: SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, SULT6B1
Mechanism and structure
[edit]The enzyme sulfotransferase catalyzes the sulfate transfer process with the use of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), which is the form of the sulfate donor in its active state.[1] Upon activation of the substrates for the catalysis, the substrate performs a nucleophilic attack on the sulfur atom from the sulfate group that has been transferred onto PAPS. This results in a transfer of the sulfate group and the creation of 3' phosphoadenosine-5-phosphate (PAP) as the products formed in the reaction. [2] Kinetic and structural studies indicate that many sulfotransferases perform their catalysis via in-line nucleophilic substitution-like mechanism.[1]
Many sulfotransferases possess conserved amino acid sequences or motifs, related to PAPS binding and catalytic activity. The central α/β fold of most cytosolic sulfotransferases contains a 5-stranded β-sheet running in a parallel fashion with surrounding α helix structures.[1] Conserved residues within the active site help orient both the sulfate donor and the acceptor substrate, contributing to catalytic efficiency and substrate specificity.[3]
Sulfotransferases are generally classified into cytosolic and membrane-associated forms. Cytosolic sulfotransferases participate primarily in the metabolism of hormones, neurotransmitters, xenobiotics, and drugs, whereas membrane-associated sulfotransferases localized in the Golgi apparatus are commonly involved in sulfation of carbohydrates, glycoproteins, and proteoglycans.[1] Structural studies using X-ray crystallography have also provided insight into substrate recognition, conformational flexibility, and inhibitor binding among sulfotransferase families.[2]
See also
[edit]- List of EC numbers (EC 2)#EC 2.8.2: Sulfotransferases
- Wikipedia:MeSH D08#MeSH D08.811.913.817 --- sulfur group transferases .28EC 2.8.29
References
[edit]- ^ a b c d e Negishi M, Pedersen LG, Petrotchenko E, et al. (2001). "Structure and function of sulfotransferases". Arch. Biochem. Biophys. 390 (2): 149–57. doi:10.1006/abbi.2001.2368. PMID 11396917.
- ^ a b c Rath VL, Verdugo D, Hemmerich S (2004). "Sulfotransferase structural biology and inhibitor discovery". Drug Discov. Today. 9 (23): 1003–11. doi:10.1016/S1359-6446(04)03273-8. PMID 15574316.
- ^ Rath VL, Verdugo D, Hemmerich S (2004). "Sulfotransferase structural biology and inhibitor discovery". Drug Discov. Today. 9 (23): 1003–1011.
External links
[edit]- Sulfotransferases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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