1p2y
From Proteopedia
(New page: 200px<br /><applet load="1p2y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p2y, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1p2y.jpg|left|200px]]<br /><applet load="1p2y" size=" | + | [[Image:1p2y.jpg|left|200px]]<br /><applet load="1p2y" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p2y, resolution 2.3Å" /> | caption="1p2y, resolution 2.3Å" /> | ||
'''CRYSTAL STRUCTURE OF CYTOCHROME P450CAM IN COMPLEX WITH (S)-(-)-NICOTINE'''<br /> | '''CRYSTAL STRUCTURE OF CYTOCHROME P450CAM IN COMPLEX WITH (S)-(-)-NICOTINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crystallographic and spectroscopic studies have been undertaken to | + | Crystallographic and spectroscopic studies have been undertaken to characterize the binding behavior of the non-native substrate nicotine in the active site of the monooxygenase hemoprotein cytochrome P450cam. Despite the existence of a theoretical model that is consistent with the observed distribution of monooxygenation products, the crystal structure of the complex indicates that the primary binding mode of nicotine is unproductive. The structure is confirmed by spectral data that indicate direct coordination of substrate pyridine nitrogen with the heme iron. This would be the proper structure for evaluating binding affinity and inhibition. Reduction of the heme from Fe(III) to Fe(II) and introduction of carbon monoxide into crystals of the nicotine-P450cam complex, to simulate molecular oxygen binding, produces reorientation of the nicotine. This orientation is the appropriate one for predicting regioselectivity and the kinetic features of substrate oxidation. While it is not clear that such complicated behavior will be exhibited for other enzyme-substrate interactions, it is clear that a single crystal structure for a given substrate-enzyme interaction may not provide a good description of the binding mode responsible for product formation. |
==About this Structure== | ==About this Structure== | ||
| - | 1P2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida] with HEM and NCT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Camphor_5-monooxygenase Camphor 5-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.15.1 1.14.15.1] Full crystallographic information is available from [http:// | + | 1P2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=NCT:'>NCT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Camphor_5-monooxygenase Camphor 5-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.15.1 1.14.15.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P2Y OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Pseudomonas putida]] | [[Category: Pseudomonas putida]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Goldstein, B | + | [[Category: Goldstein, B M.]] |
| - | [[Category: Jones, J | + | [[Category: Jones, J P.]] |
[[Category: Kim, G.]] | [[Category: Kim, G.]] | ||
[[Category: Matteson, D.]] | [[Category: Matteson, D.]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:35 2008'' |
Revision as of 12:24, 21 February 2008
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CRYSTAL STRUCTURE OF CYTOCHROME P450CAM IN COMPLEX WITH (S)-(-)-NICOTINE
Overview
Crystallographic and spectroscopic studies have been undertaken to characterize the binding behavior of the non-native substrate nicotine in the active site of the monooxygenase hemoprotein cytochrome P450cam. Despite the existence of a theoretical model that is consistent with the observed distribution of monooxygenation products, the crystal structure of the complex indicates that the primary binding mode of nicotine is unproductive. The structure is confirmed by spectral data that indicate direct coordination of substrate pyridine nitrogen with the heme iron. This would be the proper structure for evaluating binding affinity and inhibition. Reduction of the heme from Fe(III) to Fe(II) and introduction of carbon monoxide into crystals of the nicotine-P450cam complex, to simulate molecular oxygen binding, produces reorientation of the nicotine. This orientation is the appropriate one for predicting regioselectivity and the kinetic features of substrate oxidation. While it is not clear that such complicated behavior will be exhibited for other enzyme-substrate interactions, it is clear that a single crystal structure for a given substrate-enzyme interaction may not provide a good description of the binding mode responsible for product formation.
About this Structure
1P2Y is a Single protein structure of sequence from Pseudomonas putida with and as ligands. Active as Camphor 5-monooxygenase, with EC number 1.14.15.1 Full crystallographic information is available from OCA.
Reference
Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101)., Strickler M, Goldstein BM, Maxfield K, Shireman L, Kim G, Matteson DS, Jones JP, Biochemistry. 2003 Oct 21;42(41):11943-50. PMID:14556625
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