8VZJ

Crystal Structure of 2-Hydroxyacyl-CoA Lyase/Synthase DhcHACS from Dehalococcoidia bacterium in the Complex with THDP and ADP

Summary for 8VZJ

• Entry DOI: 10.2210/pdb8vzj/pdb
• Descriptor: Oxalyl-CoA decarboxylase, THIAMINE DIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: 2-hydroxyacyl-coa lyase/synthase, cacyloin condensation, sbc, eberlight, lyase
• Biological source: Dehalococcoidia bacterium
• Total number of polymer chains: 8
• Total formula weight: 487946.77

Authors

Kim, Y.,Gade, P.,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

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: 39034323
DOI: 10.1038/s42004-024-01242-y

Experimental method

X-RAY DIFFRACTION (2.7 Å)