8vzh

Crystal Structure of 2-Hydroxyacyl-CoA lyase/synthase TbHACS from Thermoflexaceae bacterium in the Complex with THDP and ADP

spinqualitylabelsall models 8vzh, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vzh is a 4 chain structure with sequence from Thermoflexaceae bacterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: ADP, CL, EDO, GOL, MG, PO4, TPP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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