8VZH
Crystal Structure of 2-Hydroxyacyl-CoA lyase/synthase TbHACS from Thermoflexaceae bacterium in the Complex with THDP and ADP
Summary for 8VZH
| Entry DOI | 10.2210/pdb8vzh/pdb |
| Descriptor | Oxalyl-CoA decarboxylase, ADENOSINE-5'-DIPHOSPHATE, THIAMINE DIPHOSPHATE, ... (9 entities in total) |
| Functional Keywords | 2-hydroxyacyl-coa lyase/synthase, oxalyly-coa decarboxylase, acyloin condensation, sbc, eberlight, lyase |
| Biological source | Thermoflexaceae bacterium |
| Total number of polymer chains | 4 |
| Total formula weight | 241171.18 |
| Authors | Kim, Y.,Maltseva, M.,Endres, M.,Lee, S.,Yoshikuni, Y.,Gonzalez, R.,Michalska, K.,Joachimiak, A. (deposition date: 2024-02-11, release date: 2024-10-02) |
| Primary citation | Kim, Y.,Lee, S.H.,Gade, P.,Nattermann, M.,Maltseva, N.,Endres, M.,Chen, J.,Wichmann, P.,Hu, Y.,Marchal, D.G.,Yoshikuni, Y.,Erb, T.J.,Gonzalez, R.,Michalska, K.,Joachimiak, A. Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family. Commun Chem, 7:160-160, 2024 Cited by PubMed Abstract: 2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-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 α-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. PubMed: 39034323DOI: 10.1038/s42004-024-01242-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
Download full validation report
