Pub. Date : 2008 Dec 18
PMID : 18563875
11 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | How do azoles inhibit cytochrome P450 enzymes? | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 2 | To examine how azole inhibitors interact with the heme active site of the cytochrome P450 enzymes, we have performed a series of density functional theory studies on azole binding. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 3 | To examine how azole inhibitors interact with the heme active site of the cytochrome P450 enzymes, we have performed a series of density functional theory studies on azole binding. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 4 | These are the first density functional studies on azole interactions with a heme center and give fundamental insight into how azoles inhibit the catalytic function of P450 enzymes. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 5 | These are the first density functional studies on azole interactions with a heme center and give fundamental insight into how azoles inhibit the catalytic function of P450 enzymes. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 6 | The calculations show that azole binding is a stepwise mechanism whereby first the water molecule from the resting state of P450 is released from the sixth binding site of the heme to create a pentacoordinated active site followed by coordination of the azole nitrogen to the heme iron. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 7 | The calculations show that azole binding is a stepwise mechanism whereby first the water molecule from the resting state of P450 is released from the sixth binding site of the heme to create a pentacoordinated active site followed by coordination of the azole nitrogen to the heme iron. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 8 | Thus, we show that release of a water molecule from the resting state of P450 enzymes to create a pentacoordinated heme will lead to a doublet to quartet spin state crossing at an Fe-OH(2) distance of approximately 3.0 A, while the azole substitution process takes place at shorter distances. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 9 | Studies with an extra hydrogen-bonded ethanol molecule in the model, mimicking the active site of the CYP121 P450, show that the resting state and azole binding structures are close in energy, which may lead to chemical equilibrium between the two structures, as indeed observed with recent protein structural studies that have demonstrated two distinct azole binding mechanisms to P450 heme. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 10 | Studies with an extra hydrogen-bonded ethanol molecule in the model, mimicking the active site of the CYP121 P450, show that the resting state and azole binding structures are close in energy, which may lead to chemical equilibrium between the two structures, as indeed observed with recent protein structural studies that have demonstrated two distinct azole binding mechanisms to P450 heme. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |
| 11 | Studies with an extra hydrogen-bonded ethanol molecule in the model, mimicking the active site of the CYP121 P450, show that the resting state and azole binding structures are close in energy, which may lead to chemical equilibrium between the two structures, as indeed observed with recent protein structural studies that have demonstrated two distinct azole binding mechanisms to P450 heme. | Azoles | cytochrome P450 family 2 subfamily B member 6 | Homo sapiens |