5i5s - Revision history

OCA at 07:23, 1 May 2024

2024-05-01T07:23:41Z

←Older revision		Revision as of 07:23, 1 May 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.		[https://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.
-
-	Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening.,Borthwick JA, Ancellin N, Bertrand SM, Bingham RP, Carter PS, Chung CW, Churcher I, Dodic N, Fournier C, Francis PL, Hobbs A, Jamieson C, Pickett SD, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Young RJ J Med Chem. 2016 Mar 24;59(6):2452-67. doi: 10.1021/acs.jmedchem.5b01607. Epub, 2016 Mar 16. PMID:26938474<ref>PMID:26938474</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5i5s" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]		*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:24, 23 August 2023

2023-08-23T08:24:07Z

←Older revision		Revision as of 08:24, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i5s' size='340' side='right'caption='[[5i5s]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='5i5s' size='340' side='right'caption='[[5i5s]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i5s]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I5S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I5S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i5s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I5S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NVU:2-(1,2-BENZOXAZOL-3-YL)ETHANOIC+ACID'>NVU</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2.06Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i5t\|5i5t]], [[5i5u\|5i5u]], [[5i5v\|5i5v]], [[5i5w\|5i5w]], [[5i5x\|5i5x]], [[5i5y\|5i5y]], [[5i60\|5i60]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NVU:2-(1,2-BENZOXAZOL-3-YL)ETHANOIC+ACID'>NVU</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCAT2, BCATM, BCT2, ECA40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5s OCA], [https://pdbe.org/5i5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i5s RCSB], [https://www.ebi.ac.uk/pdbsum/5i5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i5s ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </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=5i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5s OCA], [~~http~~://pdbe.org/5i5s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i5s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i5s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i5s ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN]] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.	+	[https://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Branched-chain-amino-acid transaminase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Somers, D]]	+	[[Category: Somers D]]
-	~~[[Category: Fold type iv]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:05, 3 June 2020

2020-06-03T07:05:39Z

←Older revision		Revision as of 07:05, 3 June 2020
Line 1:		Line 1:

	==X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BENZISOXAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.==		==X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BENZISOXAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.==
-	<StructureSection load='5i5s' size='340' side='right' caption='[[5i5s]], [[Resolution\|resolution]] 2.06Å' scene=''>	+	<StructureSection load='5i5s' size='340' side='right'caption='[[5i5s]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i5s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I5S OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I5S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i5s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I5S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I5S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NVU:2-(1,2-BENZOXAZOL-3-YL)ETHANOIC+ACID'>NVU</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NVU:2-(1,2-BENZOXAZOL-3-YL)ETHANOIC+ACID'>NVU</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i5t\|5i5t]], [[5i5u\|5i5u]], [[5i5v\|5i5v]], [[5i5w\|5i5w]], [[5i5x\|5i5x]], [[5i5y\|5i5y]], [[5i60\|5i60]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i5t\|5i5t]], [[5i5u\|5i5u]], [[5i5v\|5i5v]], [[5i5w\|5i5w]], [[5i5x\|5i5x]], [[5i5y\|5i5y]], [[5i60\|5i60]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCAT2, BCATM, BCT2, ECA40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </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=5i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5s OCA], [http://pdbe.org/5i5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i5s RCSB], [http://www.ebi.ac.uk/pdbsum/5i5s 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=5i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5s OCA], [http://pdbe.org/5i5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i5s RCSB], [http://www.ebi.ac.uk/pdbsum/5i5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i5s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5i5s" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i5s" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Branched-chain-amino-acid transaminase]]		[[Category: Branched-chain-amino-acid transaminase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Somers, D]]		[[Category: Somers, D]]
	[[Category: Fold type iv]]		[[Category: Fold type iv]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:49, 10 May 2016

2016-05-10T19:49:35Z

←Older revision		Revision as of 19:49, 10 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i5s is ~~ON HOLD~~	+	==X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BENZISOXAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.==
		+	<StructureSection load='5i5s' size='340' side='right' caption='[[5i5s]], [[Resolution\|resolution]] 2.06Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i5s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I5S FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NVU:2-(1,2-BENZOXAZOL-3-YL)ETHANOIC+ACID'>NVU</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i5t\|5i5t]], [[5i5u\|5i5u]], [[5i5v\|5i5v]], [[5i5w\|5i5w]], [[5i5x\|5i5x]], [[5i5y\|5i5y]], [[5i60\|5i60]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </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=5i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5s OCA], [http://pdbe.org/5i5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i5s RCSB], [http://www.ebi.ac.uk/pdbsum/5i5s PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN]] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.

-	~~Authors:~~ Somers, D.	+	Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening.,Borthwick JA, Ancellin N, Bertrand SM, Bingham RP, Carter PS, Chung CW, Churcher I, Dodic N, Fournier C, Francis PL, Hobbs A, Jamieson C, Pickett SD, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Young RJ J Med Chem. 2016 Mar 24;59(6):2452-67. doi: 10.1021/acs.jmedchem.5b01607. Epub, 2016 Mar 16. PMID:26938474<ref>PMID:26938474</ref>

-	~~Description: X-RAY CRYSTAL STRUCTURE AT 2~~.~~06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BENZISOXAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5i5s" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Branched-chain-amino-acid transaminase]]
	[[Category: Somers, D]]		[[Category: Somers, D]]
		+	[[Category: Fold type iv]]
		+	[[Category: Transferase]]

OCA: Protected "5i5s" [edit=sysop:move=sysop]

2016-02-26T16:49:33Z

Protected "5i5s" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:49, 26 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i5s is ON HOLD Authors: Somers, D. Description: X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE...

2016-02-26T16:49:31Z

New page: '''Unreleased structure''' The entry 5i5s is ON HOLD Authors: Somers, D. Description: X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE...

New page

'''Unreleased structure'''

The entry 5i5s is ON HOLD

Authors: Somers, D.

Description: X-RAY CRYSTAL STRUCTURE AT 2.06A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BENZISOXAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.
[[Category: Unreleased Structures]]
[[Category: Somers, D]]