5eyu - Revision history

OCA at 08:34, 12 July 2023

OCA — Wed, 12 Jul 2023 08:34:28 GMT

←Older revision		Revision as of 08:34, 12 July 2023
Line 3:		Line 3:
	<StructureSection load='5eyu' size='340' side='right'caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>		<StructureSection load='5eyu' size='340' side='right'caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus~~ aureus~~" (rosenbach 1884) zopf 1885~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5EYU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EYU FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)~~-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 1.72Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene><~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
-	<~~tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b~~></td>~~<td class="sblockDat">[[4zxu\|4zxu]]~~, ~~[[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]~~<~~/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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [https://pdbe.org/5eyu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [https://www.ebi.ac.uk/pdbsum/5eyu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eyu 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/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8]~~ </~~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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [~~http~~://pdbe.org/5eyu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5eyu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5eyu ProSAT]</span></td></tr>	+
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/Q9L4P8_STAAU Q9L4P8_STAAU]
-	Inhibition of enzyme activity by high concentrations of substrate and/or cofactor is a general phenomenon demonstrated in many enzymes, including aldehyde dehydrogenases. Here we show that the uncharacterized protein BetB (SA2613) from Staphylococcus aureus is a highly specific betaine aldehyde dehydrogenase, which exhibits substrate inhibition at concentrations of betaine aldehyde as low as 0.15 mM. In contrast, the aldehyde dehydrogenase YdcW from Escherichia coli, which is also active against betaine aldehyde, shows no inhibition by this substrate. Using the crystal structures of BetB and YdcW, we performed a structure-based mutational analysis of BetB and introduced the YdcW residues into the BetB active site. From a total of 32 mutations, those in five residues located in the substrate binding pocket (Val288, Ser290, His448, Tyr450, and Trp456) greatly reduced the substrate inhibition of BetB, whereas the double mutant protein H448F/Y450L demonstrated a complete loss of substrate inhibition. Substrate inhibition was also reduced by mutations of the semiconserved Gly234 (to Ser, Thr, or Ala) located in the BetB NAD(+) binding site, suggesting some cooperativity between the cofactor and substrate binding sites. Substrate docking analysis of the BetB and YdcW active sites revealed that the wild-type BetB can bind betaine aldehyde in both productive and nonproductive conformations, whereas only the productive binding mode can be modeled in the active sites of YdcW and the BetB mutant proteins with reduced substrate inhibition. Thus, our results suggest that the molecular mechanism of substrate inhibition of BetB is associated with the nonproductive binding of betaine aldehyde.	+
-		+
-	Structure-based mutational studies of substrate inhibition of betaine aldehyde dehydrogenase BetB from Staphylococcus aureus.,Chen C, Joo JC, Brown G, Stolnikova E, Halavaty AS, Savchenko A, Anderson WF, Yakunin AF Appl Environ Microbiol. 2014 Jul;80(13):~~3992-4002. doi: 10.1128~~/~~AEM.00215-14., Epub 2014 Apr 18. PMID:24747910<ref>PMID:24747910<~~/~~ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 5eyu" style="background-color:#fffaf0;"><~~/~~div>~~	+

	==See Also==		==See Also==
	*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]		*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Betaine-aldehyde dehydrogenase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Anderson, W F~~]]	+	[[Category: Staphylococcus aureus]]
-	[[Category: ~~Structural genomic~~]]	+	[[Category: Anderson WF]]
-	[[Category: Chen, C]]	+	[[Category: Chen C]]
-	[[Category: Halavaty~~, A S~~]]	+	[[Category: Halavaty AS]]
-	[[Category: Joo~~, J C~~]]	+	[[Category: Joo JC]]
-	[[Category: Minasov, G]]	+	[[Category: Minasov G]]
-	[[Category: Yakunin~~, A F]]~~	+	[[Category: Yakunin AF]]
-	~~[[Category: Betb]]~~	+
-	~~[[Category: Csgid]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Rossmann fold~~]]	+

OCA at 07:51, 29 April 2020

OCA — Wed, 29 Apr 2020 07:51:14 GMT

←Older revision		Revision as of 07:51, 29 April 2020
Line 1:		Line 1:

	==1.72 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==		==1.72 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==
-	<StructureSection load='5eyu' size='340' side='right' caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>	+	<StructureSection load='5eyu' size='340' side='right'caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5EYU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EYU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zxu\|4zxu]], [[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zxu\|4zxu]], [[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8] </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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [http://pdbe.org/5eyu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [http://www.ebi.ac.uk/pdbsum/5eyu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eyu ProSAT]</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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [http://pdbe.org/5eyu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [http://www.ebi.ac.uk/pdbsum/5eyu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eyu ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5eyu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5eyu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Betaine-aldehyde dehydrogenase]]		[[Category: Betaine-aldehyde dehydrogenase]]
		+	[[Category: Large Structures]]
	[[Category: Anderson, W F]]		[[Category: Anderson, W F]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 09:55, 22 November 2017

OCA — Wed, 22 Nov 2017 09:55:59 GMT

OCA at 13:42, 9 December 2015

OCA — Wed, 09 Dec 2015 13:42:47 GMT

←Older revision		Revision as of 13:42, 9 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==1.72 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==
		+	<StructureSection load='5eyu' size='340' side='right' caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EYU FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zxu\|4zxu]], [[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8] </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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [http://pdbe.org/5eyu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [http://www.ebi.ac.uk/pdbsum/5eyu PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated in the acquirement of a profound antibiotic resistance by MRSA. Betaine can be obtained from the bacterial habitat or produced intracellularly from choline via the toxic betaine aldehyde (BA) employing the choline dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early MRSA isolate COL (SaBADH) utilizes betaine aldehyde as the primary substrate and nicotinamide adenine dinucleotide (NAD(+)) as the cofactor. Surface plasmon resonance experiments revealed that the affinity of NAD(+), NADH and BA for SaBADH is affected by temperature, pH and buffer composition. Five crystal structures of the wild type and three structures of the Gly234Ser mutant of SaBADH in the apo and holo forms provide details of the molecular mechanisms of activity and substrate specificity/inhibition of this enzyme.

-	~~The entry 5eyu is ON HOLD~~	+	Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus.,Halavaty AS, Rich RL, Chen C, Joo JC, Minasov G, Dubrovska I, Winsor JR, Myszka DG, Duban M, Shuvalova L, Yakunin AF, Anderson WF Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1159-75. doi:, 10.1107/S1399004715004228. Epub 2015 Apr 25. PMID:25945581<ref>PMID:25945581</ref>

-	~~Authors: Halavaty~~, A.S.~~, Minasov, G~~.~~, Chen, C., Joo, J.C., Yakunin, A.F., Anderson, W.F., Center for Structural Genomics of Infectious Diseases~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~1.72 Angstrom resolution crystal structure of of betaine~~ aldehyde dehydrogenase ~~(betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289~~	+	<div class="pdbe-citations 5eyu" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
-	[[Category: ~~Joo~~, J.C]]	+	<references/>
-	[[Category: ~~Center For Structural Genomics Of Infectious Diseases~~]]	+	__TOC__
-	[[Category: ~~Yakunin~~, ~~A.F~~]]	+	</StructureSection>
		+	[[Category: Betaine-aldehyde dehydrogenase]]
		+	[[Category: Anderson, W F]]
		+	[[Category: Structural genomic]]
		+	[[Category: Chen, C]]
		+	[[Category: Halavaty, A S]]
		+	[[Category: Joo, J C]]
	[[Category: Minasov, G]]		[[Category: Minasov, G]]
-	[[Category: ~~Anderson~~, W.F]]	+	[[Category: Yakunin, A F]]
-	[[Category: ~~Halavaty, A.S~~]]	+	[[Category: Betb]]
-	[[Category: ~~Chen, C~~]]	+	[[Category: Csgid]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Rossmann fold]]

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

OCA — Wed, 02 Dec 2015 15:10:39 GMT

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

←Older revision

Revision as of 15:10, 2 December 2015

OCA: New page: '''Unreleased structure''' The entry 5eyu is ON HOLD Authors: Halavaty, A.S., Minasov, G., Chen, C., Joo, J.C., Yakunin, A.F., Anderson, W.F., Center for Structural Genomics of Infectio...

OCA — Wed, 02 Dec 2015 15:10:38 GMT

New page: '''Unreleased structure''' The entry 5eyu is ON HOLD Authors: Halavaty, A.S., Minasov, G., Chen, C., Joo, J.C., Yakunin, A.F., Anderson, W.F., Center for Structural Genomics of Infectio...

New page

'''Unreleased structure'''

The entry 5eyu is ON HOLD

Authors: Halavaty, A.S., Minasov, G., Chen, C., Joo, J.C., Yakunin, A.F., Anderson, W.F., Center for Structural Genomics of Infectious Diseases

Description: 1.72 Angstrom resolution crystal structure of of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289
[[Category: Unreleased Structures]]
[[Category: Joo, J.C]]
[[Category: Center For Structural Genomics Of Infectious Diseases]]
[[Category: Yakunin, A.F]]
[[Category: Minasov, G]]
[[Category: Anderson, W.F]]
[[Category: Halavaty, A.S]]
[[Category: Chen, C]]

←Older revision		Revision as of 09:55, 22 November 2017
Line 1:		Line 1:
		+
	==1.72 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==		==1.72 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) P449M point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==
	<StructureSection load='5eyu' size='340' side='right' caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>		<StructureSection load='5eyu' size='340' side='right' caption='[[5eyu]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EYU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5eyu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EYU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EYU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zxu\|4zxu]], [[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zxu\|4zxu]], [[4nea\|4nea]], [[4mpb\|4mpb]], [[5dib\|5dib]], [[4zwl\|4zwl]], [[4nu9\|4nu9]], [[4qto\|4qto]], [[4qje\|4qje]], [[4mpy\|4mpy]], [[4q92\|4q92]], [[4qn2\|4qn2]], [[5ez4\|5ez4]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Betaine-aldehyde_dehydrogenase Betaine-aldehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.8 1.2.1.8] </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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [http://pdbe.org/5eyu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [http://www.ebi.ac.uk/pdbsum/5eyu PDBsum]</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=5eyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eyu OCA], [http://pdbe.org/5eyu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eyu RCSB], [http://www.ebi.ac.uk/pdbsum/5eyu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eyu ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~When exposed to~~ high ~~osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth~~ and ~~establishes~~ a ~~new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated~~ in ~~the acquirement of a profound antibiotic resistance by MRSA~~. ~~Betaine can be obtained from~~ the ~~bacterial habitat or produced intracellularly~~ from ~~choline via the toxic~~ betaine aldehyde ~~(BA) employing the choline~~ dehydrogenase ~~and~~ betaine aldehyde ~~dehydrogenase (BADH) enzymes~~. ~~Here~~, ~~it is shown that~~ the ~~putative betaine~~ aldehyde dehydrogenase ~~SACOL2628~~ from ~~the early MRSA isolate COL (SaBADH) utilizes~~ betaine aldehyde ~~as the primary~~ substrate and ~~nicotinamide adenine dinucleotide~~ (~~NAD(+~~)~~) as~~ the ~~cofactor. Surface plasmon resonance experiments revealed that~~ the ~~affinity~~ of NAD(+), ~~NADH and BA for SaBADH is affected by temperature, pH~~ and ~~buffer composition~~. ~~Five crystal structures~~ of the wild type and ~~three structures of~~ the ~~Gly234Ser mutant of SaBADH~~ in the ~~apo and holo forms provide details~~ of the molecular ~~mechanisms~~ of ~~activity and~~ substrate ~~specificity/~~inhibition of ~~this enzyme~~.	+	Inhibition of enzyme activity by high concentrations of substrate and/or cofactor is a general phenomenon demonstrated in many enzymes, including aldehyde dehydrogenases. Here we show that the uncharacterized protein BetB (SA2613) from Staphylococcus aureus is a highly specific betaine aldehyde dehydrogenase, which exhibits substrate inhibition at concentrations of betaine aldehyde as low as 0.15 mM. In contrast, the aldehyde dehydrogenase YdcW from Escherichia coli, which is also active against betaine aldehyde, shows no inhibition by this substrate. Using the crystal structures of BetB and YdcW, we performed a structure-based mutational analysis of BetB and introduced the YdcW residues into the BetB active site. From a total of 32 mutations, those in five residues located in the substrate binding pocket (Val288, Ser290, His448, Tyr450, and Trp456) greatly reduced the substrate inhibition of BetB, whereas the double mutant protein H448F/Y450L demonstrated a complete loss of substrate inhibition. Substrate inhibition was also reduced by mutations of the semiconserved Gly234 (to Ser, Thr, or Ala) located in the BetB NAD(+) binding site, suggesting some cooperativity between the cofactor and substrate binding sites. Substrate docking analysis of the BetB and YdcW active sites revealed that the wild-type BetB can bind betaine aldehyde in both productive and nonproductive conformations, whereas only the productive binding mode can be modeled in the active sites of YdcW and the BetB mutant proteins with reduced substrate inhibition. Thus, our results suggest that the molecular mechanism of substrate inhibition of BetB is associated with the nonproductive binding of betaine aldehyde.

-	~~Structural and functional analysis~~ of betaine aldehyde dehydrogenase from Staphylococcus aureus.~~,Halavaty AS, Rich RL~~, Chen C, Joo JC, ~~Minasov~~ G, ~~Dubrovska I~~, ~~Winsor JR~~, ~~Myszka DG~~, ~~Duban M, Shuvalova L~~, Yakunin AF~~, Anderson WF Acta Crystallogr D Biol Crystallogr~~. ~~2015 May~~;71(~~Pt 5~~):~~1159~~-75. doi:, 10.~~1107~~/~~S1399004715004228~~. Epub ~~2015~~ Apr 25. PMID:~~25945581~~<ref>PMID:~~25945581~~</ref>	+	Structure-based mutational studies of substrate inhibition of betaine aldehyde dehydrogenase BetB from Staphylococcus aureus.,Chen C, Joo JC, Brown G, Stolnikova E, Halavaty AS, Savchenko A, Anderson WF, Yakunin AF Appl Environ Microbiol. 2014 Jul;80(13):3992-4002. doi: 10.1128/AEM.00215-14., Epub 2014 Apr 18. PMID:24747910<ref>PMID:24747910</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>