1LS6

Human SULT1A1 complexed with PAP and p-Nitrophenol

Summary for 1LS6

• Entry DOI: 10.2210/pdb1ls6/pdb
• Descriptor: aryl sulfotransferase, ADENOSINE-3'-5'-DIPHOSPHATE, P-NITROPHENOL, ... (4 entities in total)
• Functional Keywords: sult 1a1, pap, p-nitrophenol, positive cooperativity, two substrate binding sites, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P50225
• Total number of polymer chains: 1
• Total formula weight: 34925.73

Authors

Gamage, N.U.,Barnett, A.C.,Tresillian, M.,Latham, C.F.,Liyou, N.E.,McManus, M.E.,Martin, J.L. (deposition date: 2002-05-17, release date: 2003-08-05, Last modification date: 2024-02-14)

Primary citation

Gamage, N.U.,Duggleby, R.G.,Barnett, A.C.,Tresillian, M.,Latham, C.F.,Liyou, N.E.,McManus, M.E.,Martin, J.L.
Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition.
J.Biol.Chem., 278:7655-7662, 2003

PubMed Abstract: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, metabolizes and/or bioactivates many endogenous compounds and is implicated in a range of cancers because of its ability to modify diverse promutagen and procarcinogen xenobiotics. The crystal structure of human SULT1A1 reported here is the first sulfotransferase structure complexed with a xenobiotic substrate. An unexpected finding is that the enzyme accommodates not one but two molecules of the xenobiotic model substrate p-nitrophenol in the active site. This result is supported by kinetic data for SULT1A1 that show substrate inhibition for this small xenobiotic. The extended active site of SULT1A1 is consistent with binding of diiodothyronine but cannot easily accommodate beta-estradiol, although both are known substrates. This observation, together with evidence for a disorder-order transition in SULT1A1, suggests that the active site is flexible and can adapt its architecture to accept diverse hydrophobic substrates with varying sizes, shapes and flexibility. Thus the crystal structure of SULT1A1 provides the molecular basis for substrate inhibition and reveals the first clues as to how the enzyme sulfonates a wide variety of lipophilic compounds.

PubMed: 12471039
DOI: 10.1074/jbc.M207246200

Experimental method

X-RAY DIFFRACTION (1.9 Å)