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MetaCyc Enzyme: sulfotransferase 1A1

Gene: SULT1A1 Accession Number: G-11362 (MetaCyc)

Synonyms: STP1, STP, OK/SW-cl.88, aryl sulfotransferase 1, phenol sulfotransferase 1, phenol-sulfating phenol sulfotransferase 1, thermostable phenol sulfotransferase, TS PST1, P-PST

Species: Homo sapiens

Subunit composition of sulfotransferase 1A1 = [SULT1A1]2
         sulfotransferase 1A1 subunit = SULT1A1

Summary:
Vertebrate sulfotransferases are homodimeric [Lu09c, Weitzner09], cytosolic enzymes located in many different tissues. They are involved in the modification of endogenous compounds and xenobiotics. The major superfamilies are SULT1, SULT2 and SULT3. They utilize the sulfonate donor 3'-phosphoadenylyl-sulfate to sulfoconjugate a variety of molecules. The SULT1 family enzymes sulfoconjugate phenolic compounds, including the phenolic hydroxyl group of iodothyronines, and many have overlapping substrate specificities. In a given organ, such as liver, sulfotransferase isozymes SULT1A1 (this enzyme), SULT1A2 and SULT1A3 (see sulfotransferase 1A3/1A4 monomer) may use iodothyronines as substrates. Human SULT1A1 has the highest affinity for iodothyronines and 3'-phosphoadenylyl-sulfate, although other SULT1 isozymes and SULT2A1 are also active toward iodothyronine substrates. Reviewed in [Wu05b] and in [Lindsay08].

Sulfoconjugation is believed to accelerate the degradation of iodothyronines and may affect their bioavailability in tissues. The product of L-thyroxine sulfoconjugation, thyroxine sulfate, may be deiodinated to form the sulfate of 3,3',5-triiodothyroacetate, an inactive metabolite. Its conversion to the sulfate of active metabolite 3,5,3'-triiodo-L-thyronine by outer ring deiodination is blocked by sulfation. Sulfoconjugated iodothyronines may also serve as a reservoir for these molecules which could be recovered by the action of sulfatase enzymes in tissues, or intestinal bacteria. There is evidence that type I iododthyronine deiodinase shows accelerated deiodination of sulfoconjugated iodothyronines. Sulfoconjugation of iodothyronines in various physiological and pathological states and in fetal-maternal interactions has been studied. Reviewed in [Wu05b].

In addition to isozymes, allozymes of sulfotransferases also exist. Allozymes are allelic variants at a single locus that result in one or more amino acid changes in the enzyme. At least seven allozymes of SULT1A1 have been described and are designated as SULT1A1*1 through SULT1A1*7 (in [Li01]).

The crystal structure of human SULT1A1 has been determined [Gamage03, Gamage05, Hempel07].

Gene Citations: [Dooley98]

Map Position: [28,524,414 <- 28,542,367]

Molecular Weight of Polypeptide: 34.197 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P50225 , Entrez-gene:6817 , PhosphoSite:P50225 , Pride:P50225 , Protein Model Portal:P50225 , SMR:P50225 , String:9606.ENSP00000321988 , UniProt:P50225

Relationship Links: InterPro:IN-FAMILY:IPR000863 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:1LS6 , PDB:Structure:1Z28 , PDB:Structure:2D06 , PDB:Structure:3QVU , PDB:Structure:3QVV , PDB:Structure:3U3J , PDB:Structure:3U3K , PDB:Structure:3U3M , PDB:Structure:3U3O , PDB:Structure:3U3R , PDB:Structure:4GRA , Pfam:IN-FAMILY:PF00685

Gene-Reaction Schematic: ?

Credits:
Created 15-Jun-2009 by Fulcher CA , SRI International


Enzymatic reaction of: L-thyroxine sulfotransferase (sulfotransferase 1A1)

L-thyroxine + 3'-phosphoadenylyl-sulfate <=> adenosine 3',5'-bisphosphate + thyroxine sulfate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: thyroid hormone metabolism II (via conjugation and/or degradation)

Summary:
Recombinant human liver allozymes (see above) SULT1A1*1 and SULT1A1*2 were expressed in COS-1 cells and assayed for sulfotransferase activity using L-thyroxine as substrate. The Km values for L-thyroxine were 126 μM and 208 μM, respectively [Li01].


Enzymatic reaction of: 3,5,3'-triiodo-L-thyronine sulfotransferase (sulfotransferase 1A1)

3,5,3'-triiodo-L-thyronine + 3'-phosphoadenylyl-sulfate <=> adenosine 3',5'-bisphosphate + triiodothyronine sulfate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for 3,5,3'-triiodo-L-thyronine: L-thyroxine [Li01 ] , 3,3'-diiodothyronine [Li01 ] , 3,3',5'-triiodo-L-thyronine [Li01 ] , 3,5-diiodothyronine [Li01 ]

In Pathways: thyroid hormone metabolism II (via conjugation and/or degradation)

Summary:
Recombinant human liver allozymes (see above) SULT1A1*1 and SULT1A1*2 were expressed in COS-1 cells and assayed for sulfotransferase activity. Using 3,5,3'-triiodo-L-thyronine as substrate, sodium chloride inhibited both allozymes with IC50 values of 224 mM and 305 mM, respectively. DCNP also inhibited with IC50 values of 1.9 μM and 1.7μM, respectively. The allozymes were most active toward 3,3'-diiodothyronine, followed by 3,3',5'-triiodo-L-thyronine, 3,5,3'-triiodo-L-thyronine, L-thyroxine and 3,5-diiodothyronine. The Km values for 3,5,3'-triiodo-L-thyronine were 84.4 μM and 101.3 μM, respectively [Li01].

Inhibitors (Unknown Mechanism): 2,6-dichloro-4-nitrophenol [Li01]


References

Dooley98: Dooley TP (1998). "Cloning of the human phenol sulfotransferase gene family: three genes implicated in the metabolism of catecholamines, thyroid hormones and drugs." Chem Biol Interact 109(1-3);29-41. PMID: 9566731

Gamage03: Gamage NU, Duggleby RG, Barnett AC, Tresillian M, Latham CF, Liyou NE, McManus ME, Martin JL (2003). "Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition." J Biol Chem 278(9);7655-62. PMID: 12471039

Gamage05: Gamage NU, Tsvetanov S, Duggleby RG, McManus ME, Martin JL (2005). "The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates." J Biol Chem 280(50);41482-6. PMID: 16221673

Hempel07: Hempel N, Gamage N, Martin JL, McManus ME (2007). "Human cytosolic sulfotransferase SULT1A1." Int J Biochem Cell Biol 39(4);685-9. PMID: 17110154

Li01: Li X, Clemens DL, Cole JR, Anderson RJ (2001). "Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate." J Endocrinol 171(3);525-32. PMID: 11739018

Lindsay08: Lindsay J, Wang LL, Li Y, Zhou SF (2008). "Structure, function and polymorphism of human cytosolic sulfotransferases." Curr Drug Metab 9(2);99-105. PMID: 18288952

Lu09c: Lu LY, Chiang HP, Chen WT, Yang YS (2009). "Dimerization is responsible for the structural stability of human sulfotransferase 1A1." Drug Metab Dispos 37(5);1083-8. PMID: 19237513

Weitzner09: Weitzner B, Meehan T, Xu Q, Dunbrack RL (2009). "An unusually small dimer interface is observed in all available crystal structures of cytosolic sulfotransferases." Proteins 75(2);289-95. PMID: 19173308

Wu05b: Wu SY, Green WL, Huang WS, Hays MT, Chopra IJ (2005). "Alternate pathways of thyroid hormone metabolism." Thyroid 15(8);943-58. PMID: 16131336


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC14B.