Sandbox CYPMetabolism: Difference between revisions

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Robin Morgan

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 == Active site Volume Affects Drug Selectivity==
-Some of the factors that determine which particular CYP450 isoform metabolizes a given drug is the shape and size of its active site. As we saw above, induced fit can cause the shape of a binding pocket to change. However, induced fit may not be enough to allow a CYP with a small binding pocket to open up enough to allow larger drugs to bind. The next scene shows <scene name='60/609993/Cyp1e2/1'>CYP12E</scene> bound to the enzyme inhibitor 4-methylpyrazole (PDB code [[3e4e]]). If you will now refer back to <scene name='60/609993/Cyp3a4/18'>erythromycin bound to CYP3A4</scene>, you will notice that, in comparison to CYP1E2, there is quite a dramatic difference in the size and shape of the active site. Keep in mind that although the size and shape of each cavity can change to accommodate different drugs, CYP2E1 cannot expand to the same degree that CYP3A4 can. In fact, CYP2E1 is known to only metabolize drugs that are quite small. A few examples would be ethanol, halothane, and aniline.
+Some of the factors that determine which particular CYP450 isoform metabolizes a given drug is the shape and size of its active site. As we saw above, induced fit can cause the shape of a binding pocket to change. However, induced fit may not be enough to allow a CYP with a small binding pocket to open up enough to allow larger drugs to bind. The next scene shows
+<scene name='60/609993/Cyp1e2/1'>CYP1E2</scene> bound to the enzyme inhibitor 4-methylpyrazole (PDB code [[3e4e]]). If you will now refer back to
+<scene name='60/609993/Cyp3a4/18'>erythromycin bound to CYP3A4</scene>, you will notice that, in comparison to CYP1E2, there is quite a dramatic difference in the size and shape of the active site. Keep in mind that although the size and shape of each cavity can change to accommodate different drugs, CYP2E1 cannot expand to the same degree that CYP3A4 can. In fact, CYP2E1 is known to only metabolize drugs that are quite small. A few examples would be ethanol, halothane, and aniline.