6l3a: Difference between revisions

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-'''Unreleased structure'''
-The entry 6l3a is ON HOLD  until Paper Publication
+==Cytochrome P450 107G1 (RapN) with everolimus==
+<StructureSection load='6l3a' size='340' side='right'caption='[[6l3a]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6l3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_rapamycinicus_NRRL_5491 Streptomyces rapamycinicus NRRL 5491]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L3A FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E53:Everolimus'>E53</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=6l3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l3a OCA], [https://pdbe.org/6l3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l3a RCSB], [https://www.ebi.ac.uk/pdbsum/6l3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l3a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A0A0NSZ7_STRRN A0A0A0NSZ7_STRRN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Rapamycin is a clinically important macrolide agent with immunosuppressant and antiproliferative properties, produced by the actinobacterium, Streptomyces rapamycinicus. Two cytochrome P450 enzymes are involved in the biosynthesis of rapamycin. CYP107G1 and CYP122A2 catalyze the oxidation reactions of C27 and C9 of pre-rapamycin, respectively. To understand the structural and biochemical features of P450 enzymes in rapamycin biosynthesis, the CYP107G1 and CYP122A2 genes were cloned, their recombinant proteins were expressed in Escherichia coli, and the purified enzymes were characterized. Both enzymes displayed low spin states in the absolute spectra of ferric forms, and the titrations with rapamycin induced type I spectral changes with Kd values of 4.4 +/- 0.4 and 3.0 +/- 0.3 muM for CYP107G1 and CYP122A2, respectively. The X-ray crystal structures of CYP107G1 and its co-crystal complex with everolimus, a clinical rapamycin derivative, were determined at resolutions of 2.9 and 3.0 A, respectively. The overall structure of CYP107G1 adopts the canonical scaffold of cytochrome P450 and possesses large substrate pocket. The distal face of the heme group is exposed to solvents to accommodate macrolide access. When the structure of the everolimus-bound CYP107G1 complex (CYP107G1-Eve) was compared to that of the ligand-free CYP107G1 form, no significant conformational change was observed. Hence, CYP107G1 has a relatively rigid structure with versatile loops to accommodate a bulky substrate. The everolimus molecule is bound to the substrate-binding pocket in the shape of a squeezed donut, and its elongated structure is bound perpendicular to a planar heme plane and I-helix.
-Authors:
+Structural insights into CYP107G1 from rapamycin-producing Streptomyces rapamycinicus.,Kim V, Lim YR, Lee I, Lee JH, Han S, Pham TV, Kim H, Lee R, Kang LW, Kim D Arch Biochem Biophys. 2020 Oct 15;692:108544. doi: 10.1016/j.abb.2020.108544., Epub 2020 Aug 18. PMID:32822639<ref>PMID:32822639</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6l3a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Streptomyces rapamycinicus NRRL 5491]]
+[[Category: Kang LW]]
+[[Category: Kim DH]]
+[[Category: Km VC]]
+[[Category: Lee IH]]
+[[Category: Lee JH]]
+[[Category: Lim YR]]