8bzx

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Current revision (06:28, 19 June 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8bzx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BZX FirstGlance]. <br>
<table><tr><td colspan='2'>[[8bzx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BZX FirstGlance]. <br>
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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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SW6:2-[4-[(4-azanyl-2-methyl-pyrimidin-5-yl)methyl]-3-methyl-5-propanoyl-thiophen-2-yl]ethyl+dihydrogen+phosphate'>SW6</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SW6:2-[4-[(4-azanyl-2-methyl-pyrimidin-5-yl)methyl]-3-methyl-5-propanoyl-thiophen-2-yl]ethyl+dihydrogen+phosphate'>SW6</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=8bzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bzx OCA], [https://pdbe.org/8bzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bzx RCSB], [https://www.ebi.ac.uk/pdbsum/8bzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bzx ProSAT]</span></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=8bzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bzx OCA], [https://pdbe.org/8bzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bzx RCSB], [https://www.ebi.ac.uk/pdbsum/8bzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bzx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/A0A486V6R5_KLEPN A0A486V6R5_KLEPN] Catalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP).[HAMAP-Rule:MF_00315][https://www.uniprot.org/uniprot/A0A483FYN3_KLEPN A0A483FYN3_KLEPN] Catalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP).[HAMAP-Rule:MF_00315]
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[https://www.uniprot.org/uniprot/DXS_KLEP7 DXS_KLEP7] Catalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Thiamine diphosphate (ThDP), the bioactive form of vitamin B(1), is an essential coenzyme needed for processes of cellular metabolism in all organisms. ThDP-dependent enzymes all require ThDP as a coenzyme for catalytic activity, although individual enzymes vary significantly in substrate preferences and biochemical reactions. A popular way to study the role of these enzymes through chemical inhibition is to use thiamine/ThDP analogues, which typically feature a neutral aromatic ring in place of the positively charged thiazolium ring of ThDP. While ThDP analogues have aided work in understanding the structural and mechanistic aspects of the enzyme family, at least two key questions regarding the ligand design strategy remain unresolved: 1) which is the best aromatic ring? and 2) how can we achieve selectivity towards a given ThDP-dependent enzyme? In this work, we synthesise derivatives of these analogues covering all central aromatic rings used in the past decade and make a head-to-head comparison of all the compounds as inhibitors of several ThDP-dependent enzymes. Thus, we establish the relationship between the nature of the central ring and the inhibitory profile of these ThDP-competitive enzyme inhibitors. We also demonstrate that introducing a C2-substituent onto the central ring to explore the unique substrate-binding pocket can further improve both potency and selectivity.
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Design of thiamine analogues for inhibition of thiamine diphosphate (ThDP)-dependent enzymes: Systematic investigation through Scaffold-Hopping and C2-Functionalisation.,Chan AHY, Ho TCS, Irfan R, Hamid RAA, Rudge ES, Iqbal A, Turner A, Hirsch AKH, Leeper FJ Bioorg Chem. 2023 May 10;138:106602. doi: 10.1016/j.bioorg.2023.106602. PMID:37201323<ref>PMID:37201323</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8bzx" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

1-deoxy-D-xylulose 5-phosphate synthase from Klebsiella pneumoniae (kpDXPS),co-crystal with thiamine monophosphate analog

PDB ID 8bzx

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