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Crystal structures of SULT1A2 and SULT1A1∗3: Insights into the substrate inhibition and the role of Tyr149 in SULT1A2
- Source :
- Biochemical and Biophysical Research Communications. 396:429-434
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- 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 2.3 A 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 2.1 A 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 Km and two times lower Vmax with p-nitrophenol as substrate. These latter data imply a significant role of Tyr149 in the catalytic mechanism of SULT1A2.
- Subjects :
- Protein Conformation
Stereochemistry
medicine.medical_treatment
Phosphoadenosine Phosphosulfate
Mutant
Biophysics
Crystallography, X-Ray
Biochemistry
Catalysis
Substrate Specificity
Steroid
Nitrophenols
chemistry.chemical_compound
Residue (chemistry)
medicine
Humans
Molecular Biology
Chemistry
Mutagenesis
Substrate (chemistry)
Cell Biology
Arylsulfotransferase
Cytosol
Sulfonate
Mutation
Mutagenesis, Site-Directed
Tyrosine
Selectivity
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 396
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....0fc3026dd51e8915d0c05f1e547e93fc