5eqb: Difference between revisions

Revision as of 07:09, 22 April 2020

Crystal structure of lanosterol 14-alpha demethylase with intact transmembrane domain bound to itraconazole

Structural highlights

5eqb is a 1 chain structure with sequence from Baker's yeast. This structure supersedes the now removed PDB entry 4k0f. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	1YN, HEM
Gene:	ERG11, CYP51, YHR007C (Baker's yeast)
Activity:	Sterol 14-demethylase, with EC number 1.14.13.70
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CP51_YEAST] Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.

Publication Abstract from PubMed

Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14alpha-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance.

Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.,Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3865-70. doi:, 10.1073/pnas.1324245111. Epub 2014 Feb 3. PMID:24613931^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3865-70. doi:, 10.1073/pnas.1324245111. Epub 2014 Feb 3. PMID:24613931 doi:https://dx.doi.org/10.1073/pnas.1324245111

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3865-70. doi:, 10.1073/pnas.1324245111. Epub 2014 Feb 3. PMID:24613931 doi:https://dx.doi.org/10.1073/pnas.1324245111

[1]

@@ Line 1: / Line 1: @@
 ==Crystal structure of lanosterol 14-alpha demethylase with intact transmembrane domain bound to itraconazole==
-<StructureSection load='5eqb' size='340' side='right' caption='[[5eqb]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
+<StructureSection load='5eqb' size='340' side='right'caption='[[5eqb]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5eqb]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4k0f 4k0f]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EQB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5eqb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4k0f 4k0f]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EQB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EQB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YN:2-[(2R)-BUTAN-2-YL]-4-{4-[4-(4-{[(2R,4S)-2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZIN-1-YL]PHENYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE'>1YN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YN:2-[(2R)-BUTAN-2-YL]-4-{4-[4-(4-{[(2R,4S)-2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZIN-1-YL]PHENYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE'>1YN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERG11, CYP51, YHR007C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5eqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eqb OCA], [http://pdbe.org/5eqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eqb RCSB], [http://www.ebi.ac.uk/pdbsum/5eqb PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5eqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eqb OCA], [http://pdbe.org/5eqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eqb RCSB], [http://www.ebi.ac.uk/pdbsum/5eqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eqb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Baker's yeast]]
+[[Category: Large Structures]]
 [[Category: Sterol 14-demethylase]]
 [[Category: CSMP, Center for Structures of Membrane Proteins]]

5eqb: Difference between revisions

Revision as of 07:09, 22 April 2020

Crystal structure of lanosterol 14-alpha demethylase with intact transmembrane domain bound to itraconazole

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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