1po5: Difference between revisions

Revision as of 15:30, 21 February 2008

Structure of mammalian cytochrome P450 2B4

OverviewOverview

The xenobiotic metabolizing cytochromes P450 (P450s) are among the most versatile biological catalysts known, but knowledge of the structural basis for their broad substrate specificity has been limited. P450 2B4 has been frequently used as an experimental model for biochemical and biophysical studies of these membrane proteins. A 1.6-A crystal structure of P450 2B4 reveals a large open cleft that extends from the protein surface directly to the heme iron between the alpha-helical and beta-sheet domains without perturbing the overall P450 fold. This cleft is primarily formed by helices B' to C and F to G. The conformation of these regions is dramatically different from that of the other structurally defined mammalian P450, 2C5/3LVdH, in which the F to G and B' to C regions encapsulate one side of the active site to produce a closed form of the enzyme. The open conformation of 2B4 is trapped by reversible formation of a homodimer in which the residues between helices F and G of one molecule partially fill the open cleft of a symmetry-related molecule, and an intermolecular coordinate bond occurs between H226 and the heme iron. This dimer is observed both in solution and in the crystal. Differences between the structures of 2C5 and 2B4 suggest that defined regions of xenobiotic metabolizing P450s may adopt a substantial range of energetically accessible conformations without perturbing the overall fold. This conformational flexibility is likely to facilitate substrate access, metabolic versatility, and product egress.

About this StructureAbout this Structure

1PO5 is a Single protein structure of sequence from Oryctolagus cuniculus with as ligand. Active as Unspecific monooxygenase, with EC number 1.14.14.1 Full crystallographic information is available from OCA.

ReferenceReference

An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution., Scott EE, He YA, Wester MR, White MA, Chin CC, Halpert JR, Johnson EF, Stout CD, Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13196-201. Epub 2003 Oct 16. PMID:14563924

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-[[Image:1po5.gif|left|200px]]<br /><applet load="1po5" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1po5.gif|left|200px]]<br /><applet load="1po5" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1po5, resolution 1.6&Aring;" />
 '''Structure of mammalian cytochrome P450 2B4'''<br />
 ==Overview==
-The xenobiotic metabolizing cytochromes P450 (P450s) are among the most, versatile biological catalysts known, but knowledge of the structural, basis for their broad substrate specificity has been limited. P450 2B4 has, been frequently used as an experimental model for biochemical and, biophysical studies of these membrane proteins. A 1.6-A crystal structure, of P450 2B4 reveals a large open cleft that extends from the protein, surface directly to the heme iron between the alpha-helical and beta-sheet, domains without perturbing the overall P450 fold. This cleft is primarily, formed by helices B' to C and F to G. The conformation of these regions is, dramatically different from that of the other structurally defined, mammalian P450, 2C5/3LVdH, in which the F to G and B' to C regions, encapsulate one side of the active site to produce a closed form of the, enzyme. The open conformation of 2B4 is trapped by reversible formation of, a homodimer in which the residues between helices F and G of one molecule, partially fill the open cleft of a symmetry-related molecule, and an, intermolecular coordinate bond occurs between H226 and the heme iron. This, dimer is observed both in solution and in the crystal. Differences between, the structures of 2C5 and 2B4 suggest that defined regions of xenobiotic, metabolizing P450s may adopt a substantial range of energetically, accessible conformations without perturbing the overall fold. This, conformational flexibility is likely to facilitate substrate access, metabolic versatility, and product egress.
+The xenobiotic metabolizing cytochromes P450 (P450s) are among the most versatile biological catalysts known, but knowledge of the structural basis for their broad substrate specificity has been limited. P450 2B4 has been frequently used as an experimental model for biochemical and biophysical studies of these membrane proteins. A 1.6-A crystal structure of P450 2B4 reveals a large open cleft that extends from the protein surface directly to the heme iron between the alpha-helical and beta-sheet domains without perturbing the overall P450 fold. This cleft is primarily formed by helices B' to C and F to G. The conformation of these regions is dramatically different from that of the other structurally defined mammalian P450, 2C5/3LVdH, in which the F to G and B' to C regions encapsulate one side of the active site to produce a closed form of the enzyme. The open conformation of 2B4 is trapped by reversible formation of a homodimer in which the residues between helices F and G of one molecule partially fill the open cleft of a symmetry-related molecule, and an intermolecular coordinate bond occurs between H226 and the heme iron. This dimer is observed both in solution and in the crystal. Differences between the structures of 2C5 and 2B4 suggest that defined regions of xenobiotic metabolizing P450s may adopt a substantial range of energetically accessible conformations without perturbing the overall fold. This conformational flexibility is likely to facilitate substrate access, metabolic versatility, and product egress.
 ==About this Structure==
-PO5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with HEM as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PO5 OCA].
+PO5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=HEM:'>HEM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PO5 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Unspecific monooxygenase]]
-[[Category: Chin, C.C.]]
+[[Category: Chin, C C.]]
-[[Category: Halpert, J.R.]]
+[[Category: Halpert, J R.]]
-[[Category: He, Y.A.]]
+[[Category: He, Y A.]]
-[[Category: Johnson, E.F.]]
+[[Category: Johnson, E F.]]
-[[Category: Scott, E.E.]]
+[[Category: Scott, E E.]]
-[[Category: Stout, C.D.]]
+[[Category: Stout, C D.]]
-[[Category: Wester, M.R.]]
+[[Category: Wester, M R.]]
-[[Category: White, M.A.]]
+[[Category: White, M A.]]
 [[Category: HEM]]
 [[Category: cyp 2b4]]
@@ Line 30: / Line 30: @@
 [[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:57:48 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:43 2008''