Dynamics of water molecules in the active-site cavity of human cytochromes P450
Rydberg, Patrik LU ; Rod, Thomas LU ; Olsen, Lars and Ryde, Ulf LU
(2007)
In The Journal of Physical Chemistry Part B
111(19).
p.5445-5457
- Abstract
- We have studied the dynamics of water molecules in six crystal structures of four human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics simulations. In the crystal structures, only a few water molecules are seen and the reported sizes of the active-site cavity vary a lot. In the simulations, the cavities are completely filled with water molecules, although with similar to 20% lower density than in bulk water. The 2A6 protein differs from the other three in that it has a very small cavity with only two water molecules and no exchange with the surroundings. The other three proteins have quite big cavities, with 41 water molecules on average in 2C8 and 54-58 in 2C9 and 3A4, giving a water volume of 1500-2100 angstrom(3). The... (More)
- We have studied the dynamics of water molecules in six crystal structures of four human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics simulations. In the crystal structures, only a few water molecules are seen and the reported sizes of the active-site cavity vary a lot. In the simulations, the cavities are completely filled with water molecules, although with similar to 20% lower density than in bulk water. The 2A6 protein differs from the other three in that it has a very small cavity with only two water molecules and no exchange with the surroundings. The other three proteins have quite big cavities, with 41 water molecules on average in 2C8 and 54-58 in 2C9 and 3A4, giving a water volume of 1500-2100 angstrom(3). The two crystal structures of 2C9 differ quite appreciably, whereas those of 3A4 are quite similar. The active-site cavity is connected to the surroundings by three to six channels, through which there is a quite frequent exchange of water molecules (one molecule is exchanged every 30-200 ps), except in 2A6. Most of the channels are observed also in the crystal structures, but two to three channels in each protein open only during the simulations. There are no water molecules close to the heme iron ion in these simulations of the high-spin ferric state (the average distance to the closest water molecule is 3.3-5 angstrom), and there are few ordered water molecules in the active sites, none of which is conserved in all proteins. (Less)
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https://lup.lub.lu.se/record/664519
- author
- Rydberg, Patrik
LU
; Rod, Thomas
LU
; Olsen, Lars
and Ryde, Ulf
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Physical Chemistry Part B
- volume
- 111
- issue
- 19
- pages
- 5445 - 5457
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000246341300057
- scopus:34249829268
- pmid:17441761
- ISSN
- 1520-5207
- DOI
- 10.1021/jp070390c
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- 10f004a8-650a-4b20-bddb-c53dfbd18771 (old id 664519)
- date added to LUP
- 2016-04-01 16:00:12
- date last changed
- 2023-04-07 19:45:56
@article{10f004a8-650a-4b20-bddb-c53dfbd18771,
abstract = {{We have studied the dynamics of water molecules in six crystal structures of four human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics simulations. In the crystal structures, only a few water molecules are seen and the reported sizes of the active-site cavity vary a lot. In the simulations, the cavities are completely filled with water molecules, although with similar to 20% lower density than in bulk water. The 2A6 protein differs from the other three in that it has a very small cavity with only two water molecules and no exchange with the surroundings. The other three proteins have quite big cavities, with 41 water molecules on average in 2C8 and 54-58 in 2C9 and 3A4, giving a water volume of 1500-2100 angstrom(3). The two crystal structures of 2C9 differ quite appreciably, whereas those of 3A4 are quite similar. The active-site cavity is connected to the surroundings by three to six channels, through which there is a quite frequent exchange of water molecules (one molecule is exchanged every 30-200 ps), except in 2A6. Most of the channels are observed also in the crystal structures, but two to three channels in each protein open only during the simulations. There are no water molecules close to the heme iron ion in these simulations of the high-spin ferric state (the average distance to the closest water molecule is 3.3-5 angstrom), and there are few ordered water molecules in the active sites, none of which is conserved in all proteins.}},
author = {{Rydberg, Patrik and Rod, Thomas and Olsen, Lars and Ryde, Ulf}},
issn = {{1520-5207}},
language = {{eng}},
number = {{19}},
pages = {{5445--5457}},
publisher = {{The American Chemical Society (ACS)}},
series = {{The Journal of Physical Chemistry Part B}},
title = {{Dynamics of water molecules in the active-site cavity of human cytochromes P450}},
url = {{https://lup.lub.lu.se/search/files/135494223/98_waters_in_p450.pdf}},
doi = {{10.1021/jp070390c}},
volume = {{111}},
year = {{2007}},
}