Structural highlights
Function
[ST1A1_HUMAN] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The cytosolic sulfotransferases (SULTs) in vertebrates catalyze the sulfonation of endogenous thyroid/steroid hormones and catecholamine neurotransmitters, as well as a variety of xenobiotics, using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfonate donor. In this study, we determined the structures of SULT1A2 and an allozyme of SULT1A1, SULT1A1 *3, bound with 3'-phosphoadenosine 5'-phosphate (PAP), at 2.4 and 2.3A resolution, respectively. The conformational differences between the two structures revealed a plastic substrate-binding pocket with two channels and a switch-like substrate selectivity residue Phe247, providing clearly a structural basis for the substrate inhibition. In SULT1A2, Tyr149 extends approximately 2.1A further to the inside of the substrate-binding pocket, compared with the corresponding His149 residue in SULT1A1 *3. Site-directed mutagenesis study showed that, compared with the wild-type SULT1A2, mutant Tyr149Phe SULT1A2 exhibited a 40 times higher K(m) and two times lower V(max) with p-nitrophenol as substrate. These latter data imply a significant role of Tyr149 in the catalytic mechanism of SULT1A2.
Crystal structures of SULT1A2 and SULT1A1 *3: insights into the substrate inhibition and the role of Tyr149 in SULT1A2.,Lu J, Li H, Zhang J, Li M, Liu MY, An X, Liu MC, Chang W Biochem Biophys Res Commun. 2010 May 28;396(2):429-34. Epub 2010 Apr 22. PMID:20417180[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gamage NU, Duggleby RG, Barnett AC, Tresillian M, Latham CF, Liyou NE, McManus ME, Martin JL. Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition. J Biol Chem. 2003 Feb 28;278(9):7655-62. Epub 2002 Dec 5. PMID:12471039 doi:http://dx.doi.org/10.1074/jbc.M207246200
- ↑ Gamage NU, Tsvetanov S, Duggleby RG, McManus ME, Martin JL. The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates. J Biol Chem. 2005 Dec 16;280(50):41482-6. Epub 2005 Oct 12. PMID:16221673 doi:10.1074/jbc.M508289200
- ↑ Lu J, Li H, Zhang J, Li M, Liu MY, An X, Liu MC, Chang W. Crystal structures of SULT1A2 and SULT1A1 *3: insights into the substrate inhibition and the role of Tyr149 in SULT1A2. Biochem Biophys Res Commun. 2010 May 28;396(2):429-34. Epub 2010 Apr 22. PMID:20417180 doi:10.1016/j.bbrc.2010.04.109
