1pkf: Difference between revisions

No edit summary
No edit summary
 
(4 intermediate revisions by the same user not shown)
Line 1: Line 1:
==Crystal Structure of Epothilone D-bound Cytochrome P450epoK==
==Crystal Structure of Epothilone D-bound Cytochrome P450epoK==
<StructureSection load='1pkf' size='340' side='right' caption='[[1pkf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='1pkf' size='340' side='right'caption='[[1pkf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1pkf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"polyangium_compositum"_thaxter_1904 "polyangium compositum" thaxter 1904]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PKF FirstGlance]. <br>
<table><tr><td colspan='2'>[[1pkf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sorangium_cellulosum Sorangium cellulosum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PKF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPD:EPOTHILONE+D'>EPD</scene>, <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]] 2.1&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pkf OCA], [http://pdbe.org/1pkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pkf RCSB], [http://www.ebi.ac.uk/pdbsum/1pkf PDBsum]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPD:EPOTHILONE+D'>EPD</scene>, <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=1pkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pkf OCA], [https://pdbe.org/1pkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pkf RCSB], [https://www.ebi.ac.uk/pdbsum/1pkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pkf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/C167_SORCE C167_SORCE]] Involved in the biosynthesis of epothilones, macrolactones which have a narrow anti-fungal spectrum and microtubule-stabilizing activity. Responsible for the epooxidation of epothilones C and D to epothilones A and B, respectively.<ref>PMID:10831849</ref>
[https://www.uniprot.org/uniprot/C167_SORCE C167_SORCE] Involved in the biosynthesis of epothilones, macrolactones which have a narrow anti-fungal spectrum and microtubule-stabilizing activity. Responsible for the epooxidation of epothilones C and D to epothilones A and B, respectively.<ref>PMID:10831849</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pk/1pkf_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pk/1pkf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1pkf ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Epothilones are potential anticancer drugs that stabilize microtubules by binding to tubulin in a manner similar to paclitaxel. Cytochrome P450epoK (P450epoK), a heme containing monooxygenase involved in epothilone biosynthesis in the myxobacterium Sorangium cellulosum, catalyzes the epoxidation of epothilones C and D into epothilones A and B, respectively. The 2.10-, 1.93-, and 2.65-A crystal structures reported here for the epothilone D-bound, epothilone B-bound, and substrate-free forms, respectively, are the first crystal structures of an epothilone-binding protein. Although the substrate for P450epoK is the largest of a P450 whose x-ray structure is known, the structural changes along with substrate binding or product release are very minor and the overall fold is similar to other P450s. The epothilones are positioned with the macrolide ring roughly perpendicular to the heme plane and I helix, and the thiazole moiety provides key interactions that very likely are critical in determining substrate specificity. Interestingly, there are strong parallels between the epothilone/P450epoK and paclitaxel/tubulin interactions. Based on structural similarities, a plausible epothilone tubulin-binding mode is proposed.
Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK.,Nagano S, Li H, Shimizu H, Nishida C, Ogura H, Ortiz de Montellano PR, Poulos TL J Biol Chem. 2003 Nov 7;278(45):44886-93. Epub 2003 Aug 21. PMID:12933799<ref>PMID:12933799</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pkf" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Cytochrome P450|Cytochrome P450]]
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Polyangium compositum thaxter 1904]]
[[Category: Large Structures]]
[[Category: Li, H]]
[[Category: Sorangium cellulosum]]
[[Category: Montellano, P R.Ortiz de]]
[[Category: Li H]]
[[Category: Nagano, S]]
[[Category: Nagano S]]
[[Category: Nishida, C]]
[[Category: Nishida C]]
[[Category: Ogura, H]]
[[Category: Ogura H]]
[[Category: Poulos, T L]]
[[Category: Ortiz de Montellano PR]]
[[Category: Shimizu, H]]
[[Category: Poulos TL]]
[[Category: Cytochrome p450epok]]
[[Category: Shimizu H]]
[[Category: Heme-enzyme]]
[[Category: Oxidoreductase]]

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

OCA