2h7q
From Proteopedia
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| - | [[Image:2h7q.jpg|left|200px]] | + | [[Image:2h7q.jpg|left|200px]] |
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| - | '''Cytochrome P450cam complexed with imidazole''' | + | {{Structure |
| + | |PDB= 2h7q |SIZE=350|CAPTION= <scene name='initialview01'>2h7q</scene>, resolution 1.5Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> and <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= camC, cyp101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=303 Pseudomonas putida]) | ||
| + | }} | ||
| + | |||
| + | '''Cytochrome P450cam complexed with imidazole''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H7Q is a [ | + | 2H7Q is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7Q OCA]. |
==Reference== | ==Reference== | ||
| - | Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450(cam) by an L244A mutation., Verras A, Alian A, de Montellano PR, Protein Eng Des Sel. 2006 Nov;19(11):491-6. Epub 2006 Aug 30. PMID:[http:// | + | Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450(cam) by an L244A mutation., Verras A, Alian A, de Montellano PR, Protein Eng Des Sel. 2006 Nov;19(11):491-6. Epub 2006 Aug 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16943206 16943206] |
[[Category: Camphor 5-monooxygenase]] | [[Category: Camphor 5-monooxygenase]] | ||
[[Category: Pseudomonas putida]] | [[Category: Pseudomonas putida]] | ||
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[[Category: IMD]] | [[Category: IMD]] | ||
[[Category: active site conformation]] | [[Category: active site conformation]] | ||
| - | [[Category: azole | + | [[Category: azole drug]] |
[[Category: cytochrome p450 inhibition]] | [[Category: cytochrome p450 inhibition]] | ||
[[Category: imidazole binding]] | [[Category: imidazole binding]] | ||
[[Category: protein maleability]] | [[Category: protein maleability]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:13:41 2008'' |
Revision as of 15:13, 20 March 2008
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| , resolution 1.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | camC, cyp101 (Pseudomonas putida) | ||||||
| Activity: | Camphor 5-monooxygenase, with EC number 1.14.15.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Cytochrome P450cam complexed with imidazole
Overview
We have identified a P450(cam) mutation, L244A, that mitigates the affinity for imidazole and substituted imidazoles while maintaining a high affinity for the natural substrate camphor. The P450(cam) L244A crystal structure solved in the absence of any ligand reveals that the I-helix is displaced inwards by over 1 A in response to the cavity created by the change from leucine to alanine. Furthermore, the crystal structures of imidazole-bound P450(cam) and the 1-methylimidazole-bound P450(cam) L244A mutant reveal that the ligands have distinct binding modes in the two proteins. Whereas in wild-type P450(cam) the imidazole coordinates to the iron in an orientation roughly perpendicular to the plane of the heme, in the L244A mutant the rearranged I helix, and specifically residue Val247, forces the imidazole into an orientation almost parallel to the heme that impairs its ability to coordinate to the heme iron. As a result, the imidazole is much more weakly bound to the mutant than it is to the wild-type enzyme. Despite the constriction of the active site by the mutation, previous work with the L244A mutant has shown that it oxidizes larger substrates than the wild-type enzyme. This paradoxical situation, in which a mutation that nominally increases the active site cavity appears to decrease it, suggests that the mutation actually increases the active site maleability, allowing it to better expand to oxidize larger substrates.
About this Structure
2H7Q is a Single protein structure of sequence from Pseudomonas putida. Full crystallographic information is available from OCA.
Reference
Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450(cam) by an L244A mutation., Verras A, Alian A, de Montellano PR, Protein Eng Des Sel. 2006 Nov;19(11):491-6. Epub 2006 Aug 30. PMID:16943206
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