1ls6
From Proteopedia
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'''Human SULT1A1 complexed with PAP and p-Nitrophenol''' | '''Human SULT1A1 complexed with PAP and p-Nitrophenol''' | ||
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[[Category: McManus, M E.]] | [[Category: McManus, M E.]] | ||
[[Category: Tresillian, M.]] | [[Category: Tresillian, M.]] | ||
| - | [[Category: | + | [[Category: P-nitrophenol]] |
| - | [[Category: | + | [[Category: Pap]] |
| - | [[Category: | + | [[Category: Positive cooperativity]] |
| - | [[Category: | + | [[Category: Sult 1a1]] |
| - | [[Category: | + | [[Category: Two substrate binding site]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:14:09 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 21:14, 2 May 2008
Human SULT1A1 complexed with PAP and p-Nitrophenol
Overview
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.
About this Structure
1LS6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition., Gamage NU, Duggleby RG, Barnett AC, Tresillian M, Latham CF, Liyou NE, McManus ME, Martin JL, J Biol Chem. 2003 Feb 28;278(9):7655-62. Epub 2002 Dec 5. PMID:12471039 Page seeded by OCA on Sat May 3 00:14:09 2008
