1x8v: Difference between revisions

Revision as of 14:42, 3 May 2008

Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)

OverviewOverview

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 StructureAbout this Structure

1X8V is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

ReferenceReference

Estriol bound and ligand-free structures of sterol 14alpha-demethylase., Podust LM, Yermalitskaya LV, Lepesheva GI, Podust VN, Dalmasso EA, Waterman MR, Structure. 2004 Nov;12(11):1937-45. PMID:15530358 Page seeded by OCA on Sat May 3 14:42:51 2008

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OCA

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 [[Image:1x8v.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1x8v |SIZE=350|CAPTION= <scene name='initialview01'>1x8v</scene>, resolution 1.55&Aring;
+The line below this paragraph, containing "STRUCTURE_1x8v", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ESL:ESTRIOL'>ESL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= cyp51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
+-->
-|DOMAIN=
+{{STRUCTURE_1x8v|  PDB=1x8v  |  SCENE=  }}
-|RELATEDENTRY=[[1e9x|1E9X]], [[1ea1|1EA1]], [[1h5z|1H5Z]], [[1u13|1U13]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x8v OCA], [http://www.ebi.ac.uk/pdbsum/1x8v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x8v RCSB]</span>
-}}
 '''Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)'''
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 [[Category: Waterman, M R.]]
 [[Category: Yermalitskaya, L V.]]
-[[Category: alpha-beta]]
+[[Category: Alpha-beta]]
-[[Category: heme co-factor]]
+[[Category: Heme co-factor]]
-[[Category: protein-estriol complex]]
+[[Category: Protein-estriol complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 14:42:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:46:19 2008''