1Z29

Crystal Structures of SULT1A2 and SULT1A1*3: Implications in the bioactivation of N-hydroxy-2-acetylamino fluorine (OH-AAF)

Summary for 1Z29

• Entry DOI: 10.2210/pdb1z29/pdb
• Related: 1Z28
• Descriptor: Phenol-sulfating phenol sulfotransferase 2, CALCIUM ION, ADENOSINE-3'-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: sult1a2, pap, cation-pi interaction, plastic substrate binding pocket, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P50226
• Total number of polymer chains: 1
• Total formula weight: 34869.90

Authors

Lu, J.,Li, H.,Liu, M.C.,Zhang, J.,Li, M.,An, X.,Chang, W. (deposition date: 2005-03-07, release date: 2006-05-30, Last modification date: 2023-10-25)

Primary citation

Lu, J.,Li, H.,Zhang, J.,Li, M.,Liu, M.Y.,An, X.,Liu, M.C.,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., 396:429-434, 2010

PubMed 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 2.3A 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.

PubMed: 20417180
DOI: 10.1016/j.bbrc.2010.04.109

Experimental method

X-RAY DIFFRACTION (2.4 Å)