5kkn - Revision history

OCA at 12:40, 6 March 2024

OCA — Wed, 06 Mar 2024 12:40:49 GMT

←Older revision		Revision as of 12:40, 6 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.		[https://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein-protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.
-
-	Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats.,Harriman G, Greenwood J, Bhat S, Huang X, Wang R, Paul D, Tong L, Saha AK, Westlin WF, Kapeller R, Harwood HJ Jr Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805. doi:, 10.1073/pnas.1520686113. Epub 2016 Mar 14. PMID:26976583<ref>PMID:26976583</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5kkn" style="background-color:#fffaf0;"></div>

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

OCA at 10:48, 27 September 2023

OCA — Wed, 27 Sep 2023 10:48:30 GMT

←Older revision		Revision as of 10:48, 27 September 2023
Line 1:		Line 1:

	==Crystal structure of human ACC2 BC domain in complex with ND-646, the primary amide of ND-630==		==Crystal structure of human ACC2 BC domain in complex with ND-646, the primary amide of ND-630==
-	<StructureSection load='5kkn' size='340' side='right' caption='[[5kkn]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='5kkn' size='340' side='right'caption='[[5kkn]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kkn]] 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=5KKN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kkn]] 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=5KKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KKN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6U3:2-[1-[(2~{R})-2-(2-METHOXYPHENYL)-2-(OXAN-4-YLOXY)ETHYL]-5-METHYL-6-(1,3-OXAZOL-2-YL)-2,4-BIS(OXIDANYLIDENE)THIENO[2,3-D]PYRIMIDIN-3-YL]-2-METHYL-PROPANAMIDE'>6U3</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]] 2.6Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACACB, ACC2, ACCB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6U3:2-[1-[(2~{R})-2-(2-METHOXYPHENYL)-2-(OXAN-4-YLOXY)ETHYL]-5-METHYL-6-(1,3-OXAZOL-2-YL)-2,4-BIS(OXIDANYLIDENE)THIENO[2,3-D]PYRIMIDIN-3-YL]-2-METHYL-PROPANAMIDE'>6U3</scene></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=5kkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkn OCA], [~~http~~://pdbe.org/5kkn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5kkn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5kkn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkn 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=5kkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkn OCA], [https://pdbe.org/5kkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kkn RCSB], [https://www.ebi.ac.uk/pdbsum/5kkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN]] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.	+	[https://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5kkn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5kkn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Acetyl-CoA carboxylase 3D structures\|Acetyl-CoA carboxylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Paul, D~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Tong, L~~]]	+	[[Category: Paul D]]
-	[[Category: ~~Wang, R~~]]	+	[[Category: Tong L]]
-	[[Category: ~~Biotin-dependent carboxylase]]~~	+	[[Category: Wang R]]
-	~~[[Category: Grasp fold]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 06:11, 1 November 2017

OCA — Wed, 01 Nov 2017 06:11:30 GMT

←Older revision		Revision as of 06:11, 1 November 2017
Line 3:		Line 3:
	<StructureSection load='5kkn' size='340' side='right' caption='[[5kkn]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='5kkn' size='340' side='right' caption='[[5kkn]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kkn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kkn]] 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=5KKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KKN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6U3:2-[1-[(2~{R})-2-(2-METHOXYPHENYL)-2-(OXAN-4-YLOXY)ETHYL]-5-METHYL-6-(1,3-OXAZOL-2-YL)-2,4-BIS(OXIDANYLIDENE)THIENO[2,3-D]PYRIMIDIN-3-YL]-2-METHYL-PROPANAMIDE'>6U3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6U3:2-[1-[(2~{R})-2-(2-METHOXYPHENYL)-2-(OXAN-4-YLOXY)ETHYL]-5-METHYL-6-(1,3-OXAZOL-2-YL)-2,4-BIS(OXIDANYLIDENE)THIENO[2,3-D]PYRIMIDIN-3-YL]-2-METHYL-PROPANAMIDE'>6U3</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACACB, ACC2, ACCB ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkn OCA], [http://pdbe.org/5kkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kkn RCSB], [http://www.ebi.ac.uk/pdbsum/5kkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkn ProSAT]</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=5kkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkn OCA], [http://pdbe.org/5kkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kkn RCSB], [http://www.ebi.ac.uk/pdbsum/5kkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkn ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Paul, D]]		[[Category: Paul, D]]
	[[Category: Tong, L]]		[[Category: Tong, L]]

OCA at 11:50, 14 July 2016

OCA — Thu, 14 Jul 2016 11:50:45 GMT

←Older revision		Revision as of 11:50, 14 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5kkn is ~~ON HOLD~~	+	==Crystal structure of human ACC2 BC domain in complex with ND-646, the primary amide of ND-630==
		+	<StructureSection load='5kkn' size='340' side='right' caption='[[5kkn]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5kkn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KKN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6U3:2-[1-[(2~{R})-2-(2-METHOXYPHENYL)-2-(OXAN-4-YLOXY)ETHYL]-5-METHYL-6-(1,3-OXAZOL-2-YL)-2,4-BIS(OXIDANYLIDENE)THIENO[2,3-D]PYRIMIDIN-3-YL]-2-METHYL-PROPANAMIDE'>6U3</scene></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=5kkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkn OCA], [http://pdbe.org/5kkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kkn RCSB], [http://www.ebi.ac.uk/pdbsum/5kkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkn ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN]] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein-protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.

-	~~Authors: Wang~~, R., ~~Paul~~, D., Tong, L.	+	Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats.,Harriman G, Greenwood J, Bhat S, Huang X, Wang R, Paul D, Tong L, Saha AK, Westlin WF, Kapeller R, Harwood HJ Jr Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805. doi:, 10.1073/pnas.1520686113. Epub 2016 Mar 14. PMID:26976583<ref>PMID:26976583</ref>

-	~~Description: Crystal structure of human ACC2 BC domain in complex with ND-646~~, the ~~primary amide~~ of ND-~~630~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5kkn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Paul, D]]
	[[Category: Tong, L]]		[[Category: Tong, L]]
	[[Category: Wang, R]]		[[Category: Wang, R]]
-	[[Category: ~~Paul, D~~]]	+	[[Category: Biotin-dependent carboxylase]]
		+	[[Category: Grasp fold]]
		+	[[Category: Lyase]]

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

OCA — Wed, 13 Jul 2016 00:29:06 GMT

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

←Older revision

Revision as of 00:29, 13 July 2016

OCA: New page: '''Unreleased structure''' The entry 5kkn is ON HOLD Authors: Wang, R., Paul, D., Tong, L. Description: Crystal structure of human ACC2 BC domain in complex with ND-646, the primary am...

OCA — Wed, 13 Jul 2016 00:29:04 GMT

New page: '''Unreleased structure''' The entry 5kkn is ON HOLD Authors: Wang, R., Paul, D., Tong, L. Description: Crystal structure of human ACC2 BC domain in complex with ND-646, the primary am...

New page

'''Unreleased structure'''

The entry 5kkn is ON HOLD

Authors: Wang, R., Paul, D., Tong, L.

Description: Crystal structure of human ACC2 BC domain in complex with ND-646, the primary amide of ND-630
[[Category: Unreleased Structures]]
[[Category: Tong, L]]
[[Category: Wang, R]]
[[Category: Paul, D]]