5dib

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==2.25 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) Y450L point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==
==2.25 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) Y450L point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289==
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<StructureSection load='5dib' size='340' side='right' caption='[[5dib]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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<StructureSection load='5dib' size='340' side='right'caption='[[5dib]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5dib]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DIB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DIB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5dib]] 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=5DIB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DIB FirstGlance]. <br>
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</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></td></tr>
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</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></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">[[4mpy|4mpy]], [[4qn2|4qn2]], [[4q92|4q92]], [[4qje|4qje]], [[4qto|4qto]], [[4nu9|4nu9]], [[4zwl|4zwl]], [[4mpb|4mpb]], [[4nea|4nea]], [[4zxu|4zxu]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mpy|4mpy]], [[4qn2|4qn2]], [[4q92|4q92]], [[4qje|4qje]], [[4qto|4qto]], [[4nu9|4nu9]], [[4zwl|4zwl]], [[4mpb|4mpb]], [[4nea|4nea]], [[4zxu|4zxu]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gbsA, CH51_13935, ERS157365_02065, ERS157366_01277, ERS157367_01590, ERS157368_01276, ERS157369_01327, ERS157370_01780, ERS157371_01447, ERS157372_01660, ERS157373_01815, ERS157374_00943, ERS157376_02019, ERS157379_02102, ERS157380_01277, ERS157381_01481, ERS157382_01327, ERS157383_01276, ERS157384_01683, ERS157385_01328, ERS157386_01590, ERS157387_01983, ERS157388_01278, ERS157389_01857, ERS157390_01571, ERS157391_01874, ERS157393_01280, ERS157394_01487, ERS157395_01059, ERS157409_01038, ERS195389_01428, ERS195391_02004, ERS445052_00785 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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>
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<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=5dib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dib OCA], [http://pdbe.org/5dib PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dib RCSB], [http://www.ebi.ac.uk/pdbsum/5dib PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dib OCA], [http://pdbe.org/5dib PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dib RCSB], [http://www.ebi.ac.uk/pdbsum/5dib PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dib ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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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.
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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.
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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>
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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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 5dib" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 5dib" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Betaine-aldehyde dehydrogenase]]
[[Category: Betaine-aldehyde dehydrogenase]]
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[[Category: Large Structures]]
[[Category: Anderson, W F]]
[[Category: Anderson, W F]]
[[Category: Structural genomic]]
[[Category: Structural genomic]]

Revision as of 08:04, 8 April 2020

2.25 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) Y450L point mutant from Staphylococcus aureus in complex with NAD+ and BME-modified Cys289

PDB ID 5dib

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