Oxidation of indolic bases by cytochrome P450 and ferrous picolinate

Jankowski, Krzysztof; Delaforge, Marcel; Jaouen, Maryse; Virelizier, H.

doi:10.1155/1997/364081

Cited by 1 publication

(3 citation statements)

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“…NMR study of carboline (1) The NMR (proton and carbon-13) polydimensional studies of carboline were performed in order to compare the behavior of an aza-tetracyclic skeleton behaviour within a heme cavity to the behavior of a steroidal skeleton in the same location (relative to oxidation with CP450). This was realized by selective deuteration of carboline (1), already reported by our group [14,22,33,48]…”

Section: Methods Of Spheresmentioning

confidence: 99%

“…In our previous studies [3][4][5][6]14,22,33,47,48], we have determined that the oxidation of the indolic alkaloid β-carboline (1(R)-1,2,3,4-tetrahydro-1,2-butanopyridino [3,4-b]indole) (1) with cytochrome P450 (CYP) leads to three mono hydroxylated products: 4-hydroxy, 6-hydroxy and 7-hydroxy carbolines, with the major product being 6-hydroxy carboline. The position of hydroxylation was established by extensive deuteration studies, and by comparison to other oxidation models (such as Gif [3][4][5][6] and ferrous picolinate oxidations [47]) (also see Appendix 3).…”

Section: Introductionmentioning

confidence: 99%

“…As observed by Poulos[7,11,21,39,50,51], the specific space configuration of, e.g., camphor-oxidated iron heme and the pair of amino acids Cys 357 and Tyr 96, is necessary to achieve an oxidation 4. The Lipinski rules[2][3][4][5][6]14,22,33,40,45,[47][48][49] suggest that the substrate molecules have a molecular weight less than about 500, have a calculated log P between −1 and +5, and do not donate more than 5 hydrogen bonds nor accept more than 5 × 2 hydrogen bonds. This study is in perfect correlation with the Lipinski rules: the substrate we used had a molecular weight of 226 (well below 500) and had 3 hydrogen bonds 5.…”

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confidence: 99%

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Modeling of cytochrome P450 (Cyt P450, CYP) channels

Dako

et al. 2011

Spectroscopy

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The precise location of a substrate in cytochrome P450 (CYP) governs the orientation of the oxidation position. Such information is generally obtained from biochemical data, but modeling approaches have also been used to explain these locations. We used X-ray data and modeling techniques to distinguish between the series of putative linear or curved channels which lead the substrate from the outer side of the protein to the inner, and then into the heme pocket; these techniques were also used to identify the largest such channels. Two new methods for precisely determining the 3-D structure of proteins using X-ray crystallography were proposed in order to identify these channels: first, the use of both straight and curved channels, and second, the sphere method. These data are compared with Poulos channels, and with Caver (or Mol on line) modeling methodologies. Our methods were developed from studies of the interaction between cytochrome P450CAM(CYP101) fromPseudomonas putida(as expressed inEscherichia coli) and the indolic base β-carboline. Apart from the identification of potential access channels leading to the heme-containing active site, a new explanation was advanced for the substrate's hydroxylation position. The sphere method seems to have potential to become a general and direct method for prediction of substrate access channels from reduced- or low-resolution crystallographic data.

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Section: Methods Of Spheresmentioning

confidence: 99%