1x8v: Difference between revisions
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New page: left|200px<br /><applet load="1x8v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x8v, resolution 1.55Å" /> '''Estriol-bound and li... |
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[[Image:1x8v.jpg|left|200px]]<br /><applet load="1x8v" size=" | [[Image:1x8v.jpg|left|200px]]<br /><applet load="1x8v" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1x8v, resolution 1.55Å" /> | caption="1x8v, resolution 1.55Å" /> | ||
'''Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)'''<br /> | '''Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)'''<br /> | ||
==Overview== | ==Overview== | ||
Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol | Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes and drug targets in antifungal therapy. Here, we report CYP51 structures in ligand-free and estriol bound forms. Using estriol as a probe, we determined orientation of the substrate in the active site, elucidated protein contacts with the invariant 3beta-hydroxy group of a sterol, and identified F78 as a key discriminator between 4alpha-methylated and 4alpha,beta-dimethylated substrates. Analysis of CYP51 dynamics revealed that the C helix undergoes helix-coil transition upon binding and dissociation of a ligand. Loss of helical structure of the C helix in the ligand-free form results in an unprecedented opening of the substrate binding site. Upon binding of estriol, the BC loop loses contacts with molecular surface and tends to adopt a closed conformation. A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics. | ||
==About this Structure== | ==About this Structure== | ||
1X8V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with HEM and ESL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sterol_14-demethylase Sterol 14-demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.70 1.14.13.70] Full crystallographic information is available from [http:// | 1X8V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=ESL:'>ESL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sterol_14-demethylase Sterol 14-demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.70 1.14.13.70] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X8V OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sterol 14-demethylase]] | [[Category: Sterol 14-demethylase]] | ||
[[Category: Dalmasso, E | [[Category: Dalmasso, E A.]] | ||
[[Category: Lepesheva, G | [[Category: Lepesheva, G I.]] | ||
[[Category: Podust, L | [[Category: Podust, L M.]] | ||
[[Category: Podust, V | [[Category: Podust, V N.]] | ||
[[Category: Waterman, M | [[Category: Waterman, M R.]] | ||
[[Category: Yermalitskaya, L | [[Category: Yermalitskaya, L V.]] | ||
[[Category: ESL]] | [[Category: ESL]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: protein-estriol complex]] | [[Category: protein-estriol complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:52:16 2008'' | ||
