1x8v

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:42, 23 August 2023) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1x8v.jpg|left|200px]]
 
-
{{Structure
+
==Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)==
-
|PDB= 1x8v |SIZE=350|CAPTION= <scene name='initialview01'>1x8v</scene>, resolution 1.55&Aring;
+
<StructureSection load='1x8v' size='340' side='right'caption='[[1x8v]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=ESL:ESTRIOL'>ESL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>
+
<table><tr><td colspan='2'>[[1x8v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X8V FirstGlance]. <br>
-
|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>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
-
|GENE= cyp51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ESL:ESTRIOL'>ESL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-
|DOMAIN=
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x8v OCA], [https://pdbe.org/1x8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x8v RCSB], [https://www.ebi.ac.uk/pdbsum/1x8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x8v ProSAT]</span></td></tr>
-
|RELATEDENTRY=[[1e9x|1E9X]], [[1ea1|1EA1]], [[1h5z|1H5Z]], [[1u13|1U13]]
+
</table>
-
|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>
+
== Function ==
-
}}
+
[https://www.uniprot.org/uniprot/CP51_MYCTU CP51_MYCTU] Its precise biological substrate is not known. Catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.<ref>PMID:9756611</ref> <ref>PMID:10430874</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x8/1x8v_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1x8v ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
-
'''Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)'''
+
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<ref>PMID:15530358</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1x8v" style="background-color:#fffaf0;"></div>
-
==Overview==
+
==See Also==
-
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.
+
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
1X8V is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X8V OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
[[Category: Large Structures]]
-
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:[http://www.ncbi.nlm.nih.gov/pubmed/15530358 15530358]
+
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Single protein]]
+
[[Category: Dalmasso EA]]
-
[[Category: Sterol 14-demethylase]]
+
[[Category: Lepesheva GI]]
-
[[Category: Dalmasso, E A.]]
+
[[Category: Podust LM]]
-
[[Category: Lepesheva, G I.]]
+
[[Category: Podust VN]]
-
[[Category: Podust, L M.]]
+
[[Category: Waterman MR]]
-
[[Category: Podust, V N.]]
+
[[Category: Yermalitskaya LV]]
-
[[Category: Waterman, M R.]]
+
-
[[Category: Yermalitskaya, L V.]]
+
-
[[Category: alpha-beta]]
+
-
[[Category: heme co-factor]]
+
-
[[Category: protein-estriol complex]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:46:19 2008''
+

Current revision

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

PDB ID 1x8v

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1x8v"
Personal tools