1w0f: Difference between revisions

Revision as of 12:59, 3 May 2008

CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4

OverviewOverview

Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.

About this StructureAbout this Structure

1W0F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone., Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H, Science. 2004 Jul 30;305(5684):683-6. Epub 2004 Jul 15. PMID:15256616 Page seeded by OCA on Sat May 3 12:59:21 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1w0f.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1w0f |SIZE=350|CAPTION= <scene name='initialview01'>1w0f</scene>, resolution 2.65&Aring;
+The line below this paragraph, containing "STRUCTURE_1w0f", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Str+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1w0f|  PDB=1w0f  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0f OCA], [http://www.ebi.ac.uk/pdbsum/1w0f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w0f RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4'''
@@ Line 34: / Line 31: @@
 [[Category: Ward, A.]]
 [[Category: Williams, P A.]]
-[[Category: cytochrome p450]]
+[[Category: Cytochrome p450]]
-[[Category: electron transport]]
+[[Category: Electron transport]]
-[[Category: monooxygenase]]
+[[Category: Monooxygenase]]
-[[Category: nifedipine oxidase]]
+[[Category: Nifedipine oxidase]]
-[[Category: oxidoreductase]]
+[[Category: Oxidoreductase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 12:59:21 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:29:26 2008''