8vzf: Difference between revisions
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==Crystal Structure of 2-Hydroxyacyl-CoA Lyase/Synthase ApbHACS from Alphaproteobacteria bacterium in the Complex with THDP, Coenzyme A, and ADP== | |||
<StructureSection load='8vzf' size='340' side='right'caption='[[8vzf]], [[Resolution|resolution]] 2.36Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8vzf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Alphaproteobacteria_bacterium Alphaproteobacteria bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VZF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.36Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FYN:S-{(9R,13S,15R)-17-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-9,13,15-trihydroxy-10,10-dimethyl-13,15-dioxido-4,8-dioxo-12,14,16-trioxa-3,7-diaza-13,15-diphosphaheptadec-1-yl}+thioformate+(non-preferred+name)'>FYN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</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=8vzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vzf OCA], [https://pdbe.org/8vzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vzf RCSB], [https://www.ebi.ac.uk/pdbsum/8vzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vzf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A3C0TX30_9PROT A0A3C0TX30_9PROT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian alpha-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary alpha-carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation. | |||
Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family.,Kim Y, Lee SH, Gade P, Nattermann M, Maltseva N, Endres M, Chen J, Wichmann P, Hu Y, Marchal DG, Yoshikuni Y, Erb TJ, Gonzalez R, Michalska K, Joachimiak A Commun Chem. 2024 Jul 21;7(1):160. doi: 10.1038/s42004-024-01242-y. PMID:39034323<ref>PMID:39034323</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8vzf" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Lee | [[Category: Alphaproteobacteria bacterium]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Endres M]] | ||
[[Category: Gade P]] | |||
[[Category: Gonzalez R]] | |||
[[Category: Joachimiak A]] | |||
[[Category: Kim Y]] | |||
[[Category: Lee S]] | |||
[[Category: Michalska K]] | |||
[[Category: Yoshikuni Y]] | |||
Latest revision as of 07:00, 5 October 2024
Crystal Structure of 2-Hydroxyacyl-CoA Lyase/Synthase ApbHACS from Alphaproteobacteria bacterium in the Complex with THDP, Coenzyme A, and ADPCrystal Structure of 2-Hydroxyacyl-CoA Lyase/Synthase ApbHACS from Alphaproteobacteria bacterium in the Complex with THDP, Coenzyme A, and ADP
Structural highlights
FunctionPublication Abstract from PubMed2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian alpha-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary alpha-carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation. Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family.,Kim Y, Lee SH, Gade P, Nattermann M, Maltseva N, Endres M, Chen J, Wichmann P, Hu Y, Marchal DG, Yoshikuni Y, Erb TJ, Gonzalez R, Michalska K, Joachimiak A Commun Chem. 2024 Jul 21;7(1):160. doi: 10.1038/s42004-024-01242-y. PMID:39034323[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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