4mpb: Difference between revisions
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==1.7 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus== | ==1.7 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus== | ||
<StructureSection load='4mpb' size='340' side='right' caption='[[4mpb]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4mpb' size='340' side='right'caption='[[4mpb]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mpb]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4mpb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_COL Staphylococcus aureus subsp. aureus COL]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3ed6 3ed6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MPB FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4mpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mpb OCA], [https://pdbe.org/4mpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mpb RCSB], [https://www.ebi.ac.uk/pdbsum/4mpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mpb ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0H2X0S3_STAAC A0A0H2X0S3_STAAC] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4mpb" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4mpb" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Staphylococcus aureus subsp. aureus COL]] | ||
[[Category: Anderson | [[Category: Anderson WF]] | ||
[[Category: Dubrovska I]] | |||
[[Category: Dubrovska | [[Category: Halavaty AS]] | ||
[[Category: Halavaty | [[Category: Minasov G]] | ||
[[Category: Minasov | [[Category: Peterson SN]] | ||
[[Category: Peterson | [[Category: Shuvalova L]] | ||
[[Category: Shuvalova | [[Category: Winsor J]] | ||
[[Category: Winsor | |||
Latest revision as of 12:59, 28 December 2022
1.7 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus1.7 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus
Structural highlights
FunctionPublication Abstract from PubMedInhibition 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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