1ls6: Difference between revisions

Revision as of 14:48, 21 February 2008

Human SULT1A1 complexed with PAP and p-Nitrophenol

OverviewOverview

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 StructureAbout this Structure

1LS6 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Aryl sulfotransferase, with EC number 2.8.2.1 Full crystallographic information is available from OCA.

ReferenceReference

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 Thu Feb 21 13:47:52 2008

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OCA

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-[[Image:1ls6.gif|left|200px]]<br />
+[[Image:1ls6.gif|left|200px]]<br /><applet load="1ls6" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1ls6" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1ls6, resolution 1.90&Aring;" />
 '''Human SULT1A1 complexed with PAP and p-Nitrophenol'''<br />
 ==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.
+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==
-LS6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with A3P and NPO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aryl_sulfotransferase Aryl sulfotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.1 2.8.2.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LS6 OCA].
+LS6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=A3P:'>A3P</scene> and <scene name='pdbligand=NPO:'>NPO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aryl_sulfotransferase Aryl sulfotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.1 2.8.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LS6 OCA].
 ==Reference==
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 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Barnett, A.C.]]
+[[Category: Barnett, A C.]]
-[[Category: Gamage, N.U.]]
+[[Category: Gamage, N U.]]
-[[Category: Latham, C.F.]]
+[[Category: Latham, C F.]]
-[[Category: Liyou, N.E.]]
+[[Category: Liyou, N E.]]
-[[Category: Martin, J.L.]]
+[[Category: Martin, J L.]]
-[[Category: McManus, M.E.]]
+[[Category: McManus, M E.]]
 [[Category: Tresillian, M.]]
 [[Category: A3P]]
@@ Line 30: / Line 29: @@
 [[Category: two substrate binding sites]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:03:51 2007''
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