 |
PDBsum entry 6cpp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase(oxygenase)
|
PDB id
|
|
|
|
6cpp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structures of cytochrome p-450cam complexed with camphane, Thiocamphor, And adamantane: factors controlling p-450 substrate hydroxylation.
|
|
|
Authors
|
|
R.Raag,
T.L.Poulos.
|
|
|
Ref.
|
|
Biochemistry, 1991,
30,
2674-2684.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
X-ray crystal structures have been determined for complexes of cytochrome
P-450CAM with the substrates camphane, adamantane, and thiocamphor. Unlike the
natural substrate camphor, which hydrogen bonds to Tyr96 and is metabolized to a
single product, camphane, adamantane and thiocamphor do not hydrogen bond to the
enzyme and all are hydroxylated at multiple positions. Evidently the lack of a
substrate-enzyme hydrogen bond allows substrates greater mobility in the active
site, explaining this lower regiospecificity of metabolism as well as the
inability of these substrates to displace the distal ligand to the heme iron.
Tyr96 is a ligand, via its carbonyl oxygen atom, to a cation that is thought to
stabilize the camphor-P-450CAM complex [Poulos, T. L., Finzel, B. C., &
Howard, A. J. (1987) J. Mol. Biol. 195, 687-700]. The occupancy and temperature
factor of the cationic site are lower and higher, respectively, in the presence
of the non-hydrogen-bonding substrates investigated here than in the presence of
camphor, underscoring the relationship between cation and substrate binding.
Thiocamphor gave the most unexpected orientation in the active site of any of
the substrates we have investigated to date. The orientation of thiocamphor is
quite different from that of camphor. That is, carbons 5 and 6, at which
thiocamphor is primarily hydroxylated [Atkins, W. M., & Sligar, S. G. (1988)
J. Biol. Chem. 263, 18842-18849], are positioned near Tyr96 rather than near the
heme iron. Therefore, the crystallographically observed thiocamphor-P-450CAM
structure may correspond to a nonproductive complex. Disordered solvent has been
identified in the active site in the presence of uncoupling substrates that
channel reducing equivalents away from substrate hydroxylation toward hydrogen
peroxide and/or "excess" water production. A buried solvent molecule has also
been identified, which may promote uncoupling by moving from an internal
location to the active site in the presence of highly mobile substrates.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
X-Ray crystallographic structural studies of cytochrome p-450=CAM=+
|
|
|
Authors
|
|
R.Raag,
T.L.Poulos.
|
|
|
Ref.
|
|
TO BE PUBLISHED ...
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Crystal structure of the carbon monoxide-Substrate-Cytochrome p-450cam ternary complex.
|
|
|
Authors
|
|
R.Raag,
T.L.Poulos.
|
|
|
Ref.
|
|
Biochemistry, 1989,
28,
7586-7592.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
The structural basis for substrate-Induced changes in redox potential and spin equilibrium in cytochrome p-450cam.
|
|
|
Authors
|
|
R.Raag,
T.L.Poulos.
|
|
|
Ref.
|
|
Biochemistry, 1989,
28,
917-922.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
