1jip

<table><tr><td colspan='2'>[[1jip]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_erythreus"_(sic)_waksman_1923 "actinomyces erythreus" (sic) waksman 1923]. 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>

</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>, <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>

[[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>

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== Publication Abstract from PubMed ==

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.

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:11469860<ref>PMID:11469860</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1jip" style="background-color:#fffaf0;"></div>

[[Category: Cupp-Vickery, J R]]

[[Category: Garcia, C]]

[[Category: Hofacre, A]]

[[Category: McGee-Estrada, K]]

[[Category: P450eryf]]