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1jip

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P450eryF(A245S)/ketoconazole

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OCA

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

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-[[Image:1jip.jpg|left|200px]]
- {{Structure
+==P450eryF(A245S)/ketoconazole==
-|PDB= 1jip |SIZE=350|CAPTION= <scene name='initialview01'>1jip</scene>, resolution 2.&Aring;
+<StructureSection load='1jip' size='340' side='right'caption='[[1jip]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=KTN:CIS-1-ACETYL-4-(4-((2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)PIPERAZINE'>KTN</scene>
+<table><tr><td colspan='2'>[[1jip]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharopolyspora_erythraea Saccharopolyspora erythraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JIP FirstGlance]. <br>
-|ACTIVITY=
+</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&#8491;</td></tr>
-|GENE=
+<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>, <scene name='pdbligand=KTN:CIS-1-ACETYL-4-(4-((2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)PIPERAZINE'>KTN</scene></td></tr>
-|DOMAIN=
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jip OCA], [https://pdbe.org/1jip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jip RCSB], [https://www.ebi.ac.uk/pdbsum/1jip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jip ProSAT]</span></td></tr>
-|RELATEDENTRY=
+</table>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jip OCA], [http://www.ebi.ac.uk/pdbsum/1jip PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jip RCSB]</span>
+== Function ==
-}}
+[https://www.uniprot.org/uniprot/CPXJ_SACEN CPXJ_SACEN] Catalyzes the NADPH-dependent conversion of 6-deoxyerythronolide B (6-DEB) to erythronolide B (EB) by the insertion of an oxygen at the 6S position of 6-DEB. Requires the participation of a ferredoxin and a ferredoxin reductase for the transfer of electrons from NADPH to the monooxygenase.<ref>PMID:1732208</ref> <ref>PMID:2011746</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ji/1jip_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1jip ConSurf].
+<div style="clear:both"></div>
-'''P450eryF(A245S)/ketoconazole'''
+==See Also==
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
+== References ==
-==Overview==
+<references/>
-The azole-based P450 inhibitor ketoconazole is used to treat fungal infections and functions by blocking ergosterol biosynthesis in yeast. Ketoconazole binds to mammalian P450 enzymes and this can result in drug-drug interactions and lead to liver damage. To identify protein-drug interactions that contribute to binding specificity and affinity, we determined the crystal structure of ketoconazole complexed with P450eryF. In the P450eryF/ketoconazole structure, the azole moiety and nearby rings of ketoconzole are positioned in the active site similar to the substrate, 6-deoxyerythronolide B, with the azole nitrogen atom coordinated to the heme iron atom. The remainder of the ketoconazole molecule extends into the active-site pocket, which is occupied by water in the substrate complex. Binding of ketoconazole led to unexpected conformational changes in the I-helix. The I-helix cleft near the active site has collapsed with a helical pitch of 5.4 A compared to 6.6 A in the substrate complex. P450eryF/ketoconazole crystals soaked in 6-deoxyerythronolide B to exchange ligands exhibit a structure identical with that of the original P450eryF/substrate complex, with the I-helix cleft restored to a pitch of 6.6 A. These findings indicate that the I-helix region of P450eryF is flexible and can adopt multiple conformations. An improved understanding of the flexibility of the active-site region of cytochrome P450 enzymes is important to gain insight into determinants of ligand binding/specificity as well as to evaluate models for catalytic mechanism based on static crystal structures.
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-JIP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharopolyspora_erythraea Saccharopolyspora erythraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JIP OCA].
-==Reference==
-Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF., Cupp-Vickery JR, Garcia C, Hofacre A, McGee-Estrada K, J Mol Biol. 2001 Aug 3;311(1):101-10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11469860 11469860]
 [[Category: Saccharopolyspora erythraea]]
-[[Category: Single protein]]
+[[Category: Cupp-Vickery JR]]
-[[Category: Cupp-Vickery, J R.]]
+[[Category: Garcia C]]
-[[Category: Garcia, C.]]
+[[Category: Hofacre A]]
-[[Category: Hofacre, A.]]
+[[Category: McGee-Estrada K]]
-[[Category: McGee-Estrada, K.]]
-[[Category: azole drug]]
-[[Category: cytochrome p450]]
-[[Category: ketoconazole]]
-[[Category: p450eryf]]
-[[Category: p450eryf(a245s)]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:34:16 2008''

1jip

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P450eryF(A245S)/ketoconazole

Structural highlights

Function

Evolutionary Conservation

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