1w0e

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human cytochrome P450 3A4

Structural highlights

1w0e is a 1 chain structure with sequence from Homo sapiens. The October 2006 RCSB PDB Molecule of the Month feature on Cytochrome p450 by David S. Goodsell is 10.2210/rcsb_pdb/mom_2006_10. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CP3A4_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Miyazawa M, Shindo M, Shimada T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab Dispos. 2001 Feb;29(2):200-5. PMID:11159812
↑ Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science. 2004 Jul 30;305(5684):683-6. Epub 2004 Jul 15. PMID:15256616 doi:http://dx.doi.org/10.1126/science.1099736

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w0e"

@@ Line 3: / Line 3: @@
 <StructureSection load='1w0e' size='340' side='right'caption='[[1w0e]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1w0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. The October 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Cytochrome p450''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_10 10.2210/rcsb_pdb/mom_2006_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1w0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The October 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Cytochrome p450''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_10 10.2210/rcsb_pdb/mom_2006_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w0f|1w0f]], [[1w0g|1w0g]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0e OCA], [https://pdbe.org/1w0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0e RCSB], [https://www.ebi.ac.uk/pdbsum/1w0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0e ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 37: @@
 </StructureSection>
 [[Category: Cytochrome p450]]
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: RCSB PDB Molecule of the Month]]
-[[Category: Angove, H C]]
+[[Category: Angove HC]]
-[[Category: Cosme, J]]
+[[Category: Cosme J]]
-[[Category: Day, P J]]
+[[Category: Day PJ]]
-[[Category: Jhoti, H]]
+[[Category: Jhoti H]]
-[[Category: Tickle, I J]]
+[[Category: Tickle IJ]]
-[[Category: Vinkovic, D M]]
+[[Category: Vinkovic DM]]
-[[Category: Vonrhein, C]]
+[[Category: Vonrhein C]]
-[[Category: Ward, A]]
+[[Category: Ward A]]
-[[Category: Williams, P A]]
+[[Category: Williams PA]]
-[[Category: Electron transport]]
-[[Category: Monooxygenase]]
-[[Category: Nifedipine oxidase]]
-[[Category: Oxidoreductase]]

1w0e

From Proteopedia

Current revision

Crystal structure of human cytochrome P450 3A4

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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