OCA at 16:35, 29 November 2023

OCA — Wed, 29 Nov 2023 16:35:23 GMT

←Older revision		Revision as of 16:35, 29 November 2023
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	==PHGDH covalently linked to oridonin==		==PHGDH covalently linked to oridonin==
-	<StructureSection load='7dkm' size='340' side='right'caption='[[7dkm]]' scene=''>	+	<StructureSection load='7dkm' size='340' side='right'caption='[[7dkm]], [[Resolution\|resolution]] 1.70Å' 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=7DKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DKM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7dkm]] 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=7DKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DKM 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=7dkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dkm OCA], [https://pdbe.org/7dkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dkm RCSB], [https://www.ebi.ac.uk/pdbsum/7dkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dkm ProSAT]</span></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]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ODN:(1BETA,6BETA,7BETA,8ALPHA,9BETA,10ALPHA,13ALPHA,14R,16BETA)-1,6,7,14-TETRAHYDROXY-7,20-EPOXYKAURAN-15-ONE'>ODN</scene></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=7dkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dkm OCA], [https://pdbe.org/7dkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dkm RCSB], [https://www.ebi.ac.uk/pdbsum/7dkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dkm ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[https://omim.org/entry/601815 601815]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The rate-limiting serine biogenesis enzyme PHGDH is overexpressed in cancers. Both serine withdrawal and genetic/pharmacological inhibition of PHGDH have demonstrated promising tumor-suppressing activities. However, the enzyme properties of PHGDH are not well understood and the discovery of PHGDH inhibitors is still in its infancy. Here, oridonin was identified from a natural product library as a new PHGDH inhibitor. The crystal structure of PHGDH in complex with oridonin revealed a new allosteric site. The binding of oridonin to this site reduced the activity of the enzyme by relocating R54, a residue involved in substrate binding. Mutagenesis studies showed that PHGDH activity was very sensitive to cysteine mutations, especially those in the substrate binding domain. Conjugation of oridonin and other reported covalent PHGDH inhibitors to these sites will therefore inhibit PHGDH. In addition to being inhibited enzymatically, PHGDH can also be inhibited by protein aggregation and proteasome-mediated degradation. Several tested PHGDH cancer mutants showed altered enzymatic activity, which can be explained by protein structure and stability. Overall, the above studies present new biophysical and biochemical insights into PHGDH and may facilitate the future design of PHGDH inhibitors.
		+
		+	Biophysical and biochemical properties of PHGDH revealed by studies on PHGDH inhibitors.,Tan Y, Zhou X, Gong Y, Gou K, Luo Y, Jia D, Dai L, Zhao Y, Sun Q Cell Mol Life Sci. 2021 Dec 31;79(1):27. doi: 10.1007/s00018-021-04022-2. PMID:34971423<ref>PMID:34971423</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7dkm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoglycerate dehydrogenase\|Phosphoglycerate dehydrogenase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Lei Y]]		[[Category: Lei Y]]
	[[Category: Sun Q]]		[[Category: Sun Q]]

OCA at 06:57, 2 February 2022

OCA — Wed, 02 Feb 2022 06:57:58 GMT

←Older revision		Revision as of 06:57, 2 February 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7dkm ~~is ON HOLD until Feb 25 2023~~	+	==PHGDH covalently linked to oridonin==
-		+	<StructureSection load='7dkm' size='340' side='right'caption='[[7dkm]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DKM 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=7dkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dkm OCA], [https://pdbe.org/7dkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dkm RCSB], [https://www.ebi.ac.uk/pdbsum/7dkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dkm ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lei Y]]
		+	[[Category: Sun Q]]

OCA at 12:36, 3 November 2021

OCA — Wed, 03 Nov 2021 12:36:15 GMT

←Older revision		Revision as of 12:36, 3 November 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7dkm is ON HOLD until ~~Paper Publication~~	+	The entry 7dkm is ON HOLD until Feb 25 2023

	Authors:		Authors:

OCA at 05:29, 24 February 2021

OCA — Wed, 24 Feb 2021 05:29:20 GMT

←Older revision		Revision as of 05:29, 24 February 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7dkm is ON HOLD	+	The entry 7dkm is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7dkm" [edit=sysop:move=sysop]

OCA — Wed, 02 Dec 2020 05:43:33 GMT

Protected "7dkm" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 2 December 2020

OCA: New page: '''Unreleased structure''' The entry 7dkm is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 02 Dec 2020 05:43:32 GMT

New page: '''Unreleased structure''' The entry 7dkm is ON HOLD Authors: Description: Category: Unreleased Structures

New page