6te7 - Revision history

OCA at 13:00, 24 January 2024

OCA — Wed, 24 Jan 2024 13:00:36 GMT

←Older revision		Revision as of 13:00, 24 January 2024
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	<StructureSection load='6te7' size='340' side='right'caption='[[6te7]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='6te7' size='340' side='right'caption='[[6te7]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6te7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus~~ tuberculosis~~" (zopf 1883) klein 1884~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TE7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6te7]] 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=6TE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TE7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=N55:2-chloranyl-4-[4-[(1~{R})-1-imidazol-1-ylprop-2-enyl]phenyl]phenol'>N55</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.5000182Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">cyp121, MT2336 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=N55:2-chloranyl-4-[4-[(1~{R})-1-imidazol-1-ylprop-2-enyl]phenyl]phenol'>N55</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mycocyclosin_synthase Mycocyclosin synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.19.70 1.14.19.70] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6te7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6te7 OCA], [https://pdbe.org/6te7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6te7 RCSB], [https://www.ebi.ac.uk/pdbsum/6te7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6te7 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6te7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6te7 OCA], [https://pdbe.org/6te7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6te7 RCSB], [https://www.ebi.ac.uk/pdbsum/6te7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6te7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~CP121_MYCTO CP121_MYCTO~~]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity).	+	[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6te7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6te7" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mycocyclosin synthase~~]]	+	[[Category: Mycobacterium tuberculosis]]
-	[[Category: Adam, S]]	+	[[Category: Adam S]]
-	[[Category: Koehnke, J]]	+	[[Category: Koehnke J]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Cyp121]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 09:59, 8 December 2021

OCA — Wed, 08 Dec 2021 09:59:07 GMT

←Older revision		Revision as of 09:59, 8 December 2021
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	==The structure of CYP121 in complex with inhibitor S2==		==The structure of CYP121 in complex with inhibitor S2==
-	<StructureSection load='6te7' size='340' side='right'caption='[[6te7]]' scene=''>	+	<StructureSection load='6te7' size='340' side='right'caption='[[6te7]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TE7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6te7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TE7 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6te7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6te7 OCA], [https://pdbe.org/6te7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6te7 RCSB], [https://www.ebi.ac.uk/pdbsum/6te7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6te7 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=N55:2-chloranyl-4-[4-[(1~{R})-1-imidazol-1-ylprop-2-enyl]phenyl]phenol'>N55</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">cyp121, MT2336 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mycocyclosin_synthase Mycocyclosin synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.19.70 1.14.19.70] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6te7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6te7 OCA], [https://pdbe.org/6te7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6te7 RCSB], [https://www.ebi.ac.uk/pdbsum/6te7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6te7 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/CP121_MYCTO CP121_MYCTO]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	CYP121 of Mycobacterium tuberculosis (Mtb) is an essential target for the development of novel potent drugs against tuberculosis (TB). Besides known antifungal azoles, further compounds of the azole class were recently identified as CYP121 inhibitors with antimycobacterial activity. Herein, we report the screening of a similarity-oriented library based on the former hit compound, the evaluation of affinity toward CYP121, and activity against M. bovis BCG. The results enabled a comprehensive SAR study, which was extended through the synthesis of promising compounds and led to the identification of favorable features for affinity and/or activity and hit compounds with 2.7-fold improved potency. Mode of action studies show that the hit compounds inhibit substrate conversion and highlighted CYP121 as the main antimycobacterial target of our compounds. Exemplified complex crystal structures of CYP121 with three inhibitors reveal a common binding site. Engaging in both hydrophobic interactions as well as hydrogen bonding to the sixth iron ligand, our compounds block a solvent channel leading to the active site heme. Additionally, we report the first CYP inhibitors that are able to reduce the intracellular replication of M. bovis BCG in macrophages, emphasizing their potential as future drug candidates against TB.
		+
		+	Structure-Activity Relationship and Mode-Of-Action Studies Highlight 1-(4-Biphenylylmethyl)-1H-imidazole-Derived Small Molecules as Potent CYP121 Inhibitors.,Walter I, Adam S, Gentilini MV, Kany AM, Brengel C, Thomann A, Sparwasser T, Kohnke J, Hartmann RW ChemMedChem. 2021 Sep 16;16(18):2786-2801. doi: 10.1002/cmdc.202100283. Epub 2021, Jun 22. PMID:34010508<ref>PMID:34010508</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6te7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Adam S]]	+	[[Category: Mycocyclosin synthase]]
-	[[Category: Koehnke J]]	+	[[Category: Adam, S]]
		+	[[Category: Koehnke, J]]
		+	[[Category: Complex]]
		+	[[Category: Cyp121]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]

OCA at 09:15, 26 May 2021

OCA — Wed, 26 May 2021 09:15:33 GMT

←Older revision		Revision as of 09:15, 26 May 2021
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-	'''Unreleased structure'''

-	The ~~entry~~ 6te7 ~~is ON HOLD until Paper Publication~~	+	==The structure of CYP121 in complex with inhibitor S2==
-		+	<StructureSection load='6te7' size='340' side='right'caption='[[6te7]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TE7 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6te7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6te7 OCA], [https://pdbe.org/6te7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6te7 RCSB], [https://www.ebi.ac.uk/pdbsum/6te7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6te7 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Adam S]]
		+	[[Category: Koehnke J]]

OCA at 06:12, 22 July 2020

OCA — Wed, 22 Jul 2020 06:12:45 GMT

←Older revision		Revision as of 06:12, 22 July 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6te7 is ON HOLD	+	The entry 6te7 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6te7" [edit=sysop:move=sysop]

OCA — Wed, 20 Nov 2019 13:39:14 GMT

Protected "6te7" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:39, 20 November 2019

OCA: New page: '''Unreleased structure''' The entry 6te7 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 20 Nov 2019 13:39:13 GMT

New page: '''Unreleased structure''' The entry 6te7 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6te7 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]