1w0f: Difference between revisions

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==Overview==

Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds, and xenobiotics, such as pollutants, environmental compounds, and drug, molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the, oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450, 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms, combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate, progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either, compound. An unexpected peripheral binding site is identified, located, above a phenylalanine cluster, which may be involved in the initial, recognition of substrates or allosteric effectors.

Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Angove, H.C.]]

[[Category: Angove, H C.]]

[[Category: Cosme, J.]]

[[Category: Day, P.J.]]

[[Category: Day, P J.]]

[[Category: Jhoti, H.]]

[[Category: Tickle, I.J.]]

[[Category: Tickle, I J.]]

[[Category: Vinkovic, D.M.]]

[[Category: Vinkovic, D M.]]

[[Category: Vonrhein, C.]]

[[Category: Ward, A.]]

[[Category: Williams, P.A.]]

[[Category: Williams, P A.]]

[[Category: HEM]]

[[Category: STR]]

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[[Category: oxidoreductase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun~~ Feb ~~3 10~~:17:46 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:14 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds, and xenobiotics, such as pollutants, environmental compounds, and drug, molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the, oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450, 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms, combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate, progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either, compound. An unexpected peripheral binding site is identified, located, above a phenylalanine cluster, which may be involved in the initial, recognition of substrates or allosteric effectors.
+Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Angove, H.C.]]
+[[Category: Angove, H C.]]
 [[Category: Cosme, J.]]
-[[Category: Day, P.J.]]
+[[Category: Day, P J.]]
 [[Category: Jhoti, H.]]
-[[Category: Tickle, I.J.]]
+[[Category: Tickle, I J.]]
-[[Category: Vinkovic, D.M.]]
+[[Category: Vinkovic, D M.]]
 [[Category: Vonrhein, C.]]
 [[Category: Ward, A.]]
-[[Category: Williams, P.A.]]
+[[Category: Williams, P A.]]
 [[Category: HEM]]
 [[Category: STR]]
@@ Line 30: / Line 30: @@
 [[Category: oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:17:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:14 2008''