OCA at 08:07, 11 October 2023

OCA — Wed, 11 Oct 2023 08:07:35 GMT

←Older revision		Revision as of 08:07, 11 October 2023
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	==Crystal structure of glucose-6-phosphate dehydrogenase V394L mutant in complex with catalytic NADP+==		==Crystal structure of glucose-6-phosphate dehydrogenase V394L mutant in complex with catalytic NADP+==
-	<StructureSection load='6vaq' size='340' side='right'caption='[[6vaq]]' scene=''>	+	<StructureSection load='6vaq' size='340' side='right'caption='[[6vaq]], [[Resolution\|resolution]] 2.95Å' 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=6VAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VAQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vaq]] is a 1 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=6VAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VAQ 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=6vaq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vaq OCA], [https://pdbe.org/6vaq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vaq RCSB], [https://www.ebi.ac.uk/pdbsum/6vaq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vaq 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]] 2.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6vaq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vaq OCA], [https://pdbe.org/6vaq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vaq RCSB], [https://www.ebi.ac.uk/pdbsum/6vaq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vaq ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:[https://omim.org/entry/305900 305900]. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.<ref>PMID:1611091</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common blood disorder, presenting multiple symptoms, including hemolytic anemia. It affects 400 million people worldwide, with more than 160 single mutations reported in G6PD. The most severe mutations (about 70) are classified as class I, leading to more than 90% loss of activity of the wild-type G6PD. The crystal structure of G6PD reveals these mutations are located away from the active site, concentrating around the noncatalytic NADP(+)-binding site and the dimer interface. However, the molecular mechanisms of class I mutant dysfunction have remained elusive, hindering the development of efficient therapies. To resolve this, we performed integral structural characterization of five G6PD mutants, including four class I mutants, associated with the noncatalytic NADP(+) and dimerization, using crystallography, small-angle X-ray scattering (SAXS), cryogenic electron microscopy (cryo-EM), and biophysical analyses. Comparisons with the structure and properties of the wild-type enzyme, together with molecular dynamics simulations, bring forward a universal mechanism for this severe G6PD deficiency due to the class I mutations. We highlight the role of the noncatalytic NADP(+)-binding site that is crucial for stabilization and ordering two beta-strands in the dimer interface, which together communicate these distant structural aberrations to the active site through a network of additional interactions. This understanding elucidates potential paths for drug development targeting G6PD deficiency.
		+
		+	Long-range structural defects by pathogenic mutations in most severe glucose-6-phosphate dehydrogenase deficiency.,Horikoshi N, Hwang S, Gati C, Matsui T, Castillo-Orellana C, Raub AG, Garcia AA, Jabbarpour F, Batyuk A, Broweleit J, Xiang X, Chiang A, Broweleit R, Vohringer-Martinez E, Mochly-Rosen D, Wakatsuki S Proc Natl Acad Sci U S A. 2021 Jan 26;118(4). pii: 2022790118. doi:, 10.1073/pnas.2022790118. PMID:33468660<ref>PMID:33468660</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vaq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glucose 6-phosphate dehydrogenase\|Glucose 6-phosphate dehydrogenase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Horikoshi N]]		[[Category: Horikoshi N]]
	[[Category: Mochly-Rosen D]]		[[Category: Mochly-Rosen D]]
	[[Category: Wakatsuki S]]		[[Category: Wakatsuki S]]

OCA at 07:54, 27 January 2021

OCA — Wed, 27 Jan 2021 07:54:07 GMT

←Older revision		Revision as of 07:54, 27 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6vaq is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of glucose-6-phosphate dehydrogenase V394L mutant in complex with catalytic NADP+==
-		+	<StructureSection load='6vaq' size='340' side='right'caption='[[6vaq]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VAQ 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=6vaq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vaq OCA], [https://pdbe.org/6vaq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vaq RCSB], [https://www.ebi.ac.uk/pdbsum/6vaq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vaq ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Horikoshi N]]
		+	[[Category: Mochly-Rosen D]]
		+	[[Category: Wakatsuki S]]

OCA at 05:15, 4 November 2020

OCA — Wed, 04 Nov 2020 05:15:41 GMT

←Older revision		Revision as of 05:15, 4 November 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 04:19, 7 October 2020

OCA — Wed, 07 Oct 2020 04:19:40 GMT

←Older revision		Revision as of 04:19, 7 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6vaq is ON HOLD ~~until Paper Publication~~	+	The entry 6vaq is ON HOLD

	Authors:		Authors:

OCA at 13:31, 29 January 2020

OCA — Wed, 29 Jan 2020 13:31:44 GMT

←Older revision		Revision as of 13:31, 29 January 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 25 Dec 2019 07:36:45 GMT

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

←Older revision

Revision as of 07:36, 25 December 2019

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

OCA — Wed, 25 Dec 2019 07:36:43 GMT

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

New page

'''Unreleased structure'''

The entry 6vaq is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]