6hg1 - Revision history

OCA at 09:00, 19 December 2018

2018-12-19T09:00:39Z

←Older revision		Revision as of 09:00, 19 December 2018
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	<StructureSection load='6hg1' size='340' side='right' caption='[[6hg1]], [[Resolution\|resolution]] 2.12Å' scene=''>		<StructureSection load='6hg1' size='340' side='right' caption='[[6hg1]], [[Resolution\|resolution]] 2.12Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hg1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hg1]] is a 1 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=6HG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CAD ([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=6hg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg1 OCA], [http://pdbe.org/6hg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg1 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=6hg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg1 OCA], [http://pdbe.org/6hg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg1 ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Cano-Ochoa, F Del]]		[[Category: Cano-Ochoa, F Del]]
	[[Category: Ramon-Maiques, S]]		[[Category: Ramon-Maiques, S]]

OCA at 06:04, 24 October 2018

2018-10-24T06:04:08Z

←Older revision		Revision as of 06:04, 24 October 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6hg1 is ~~ON HOLD until Paper~~ Publication	+	==Hybrid dihydroorotase domain of human CAD with E. coli flexible loop in apo state==
		+	<StructureSection load='6hg1' size='340' side='right' caption='[[6hg1]], [[Resolution\|resolution]] 2.12Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hg1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=6hg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg1 OCA], [http://pdbe.org/6hg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg1 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PYR1_HUMAN PYR1_HUMAN]] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The dihydroorotase (DHOase) domain of the multifunctional protein carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) catalyzes the third step in the de novo biosynthesis of pyrimidine nucleotides in animals. The crystal structure of the DHOase domain of human CAD (huDHOase) revealed that, despite evolutionary divergence, its active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site. Here, we combined mutagenic, structural, biochemical, and molecular dynamics analyses to characterize the function of the flexible loop in the activity of CAD's DHOase domain. A huDHOase chimera bearing the E. coli DHOase flexible loop was inactive, suggesting the presence of distinctive elements in the flexible loop of huDHOase that cannot be replaced by the bacterial sequence. We pinpoint Phe-1563, a residue absolutely conserved at the tip of the flexible loop in CAD's DHOase domain, as a critical element for the conformational equilibrium between the two catalytic states of the protein. Substitutions of Phe-1563 with Ala, Leu or Thr prevented the closure of the flexible loop and inactivated the protein, whereas substitution with Tyr enhanced the interactions of the loop in the closed position and reduced fluctuations and the reaction rate. Our results confirm the importance of the flexible loop in CAD's DHOase domain and explain the key role of Phe-1563 in configuring the active site and in promoting substrate strain and catalysis.

-	~~Authors: Ramon~~-~~Maiques, S~~., Del Cano-Ochoa, F.	+	Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD.,Del Cano-Ochoa F, Grande-Garcia A, Reverte-Lopez M, D'Abramo M, Ramon-Maiques S J Biol Chem. 2018 Oct 12. pii: RA118.005494. doi: 10.1074/jbc.RA118.005494. PMID:30315107<ref>PMID:30315107</ref>

-	~~Description: Hybrid dihydroorotase domain~~ of ~~human CAD with E~~. ~~coli flexible loop in apo state~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Del~~ Cano-Ochoa, F]]	+	<div class="pdbe-citations 6hg1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cano-Ochoa, F Del]]
	[[Category: Ramon-Maiques, S]]		[[Category: Ramon-Maiques, S]]
		+	[[Category: Biosynthetic protein]]
		+	[[Category: Cad]]
		+	[[Category: Carboxylated lysine]]
		+	[[Category: De novo pyrimidine biosynthesis]]
		+	[[Category: Tim-barrel]]

OCA at 06:11, 17 October 2018

2018-10-17T06:11:52Z

←Older revision		Revision as of 06:11, 17 October 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hg1 is ON HOLD	+	The entry 6hg1 is ON HOLD until Paper Publication

	Authors: Ramon-Maiques, S., Del Cano-Ochoa, F.		Authors: Ramon-Maiques, S., Del Cano-Ochoa, F.

OCA: Protected "6hg1" [edit=sysop:move=sysop]

2018-08-29T06:00:15Z

Protected "6hg1" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:00, 29 August 2018

OCA: New page: '''Unreleased structure''' The entry 6hg1 is ON HOLD Authors: Ramon-Maiques, S., Del Cano-Ochoa, F. Description: Hybrid dihydroorotase domain of human CAD with E. coli flexible loop in...

2018-08-29T06:00:14Z

New page: '''Unreleased structure''' The entry 6hg1 is ON HOLD Authors: Ramon-Maiques, S., Del Cano-Ochoa, F. Description: Hybrid dihydroorotase domain of human CAD with E. coli flexible loop in...

New page

'''Unreleased structure'''

The entry 6hg1 is ON HOLD

Authors: Ramon-Maiques, S., Del Cano-Ochoa, F.

Description: Hybrid dihydroorotase domain of human CAD with E. coli flexible loop in apo state
[[Category: Unreleased Structures]]
[[Category: Del Cano-Ochoa, F]]
[[Category: Ramon-Maiques, S]]