1jip: Difference between revisions
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|PDB= 1jip |SIZE=350|CAPTION= <scene name='initialview01'>1jip</scene>, resolution 2.Å | |PDB= 1jip |SIZE=350|CAPTION= <scene name='initialview01'>1jip</scene>, resolution 2.Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> | |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> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|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> | |||
}} | }} | ||
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[[Category: Hofacre, A.]] | [[Category: Hofacre, A.]] | ||
[[Category: McGee-Estrada, K.]] | [[Category: McGee-Estrada, K.]] | ||
[[Category: azole drug]] | [[Category: azole drug]] | ||
[[Category: cytochrome p450]] | [[Category: cytochrome p450]] | ||
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[[Category: p450eryf(a245s)]] | [[Category: p450eryf(a245s)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:34:16 2008'' | ||
Revision as of 21:34, 30 March 2008
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| , resolution 2.Å | |||||||
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| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
P450eryF(A245S)/ketoconazole
OverviewOverview
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.
About this StructureAbout this Structure
1JIP is a Single protein structure of sequence from Saccharopolyspora erythraea. Full crystallographic information is available from OCA.
ReferenceReference
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
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