7P9A

Structure of cyclohex-1-ene-1-carboxyl-CoA dehydrogenase complexed with cyclohex-1,5-diene-1-carboxyl-CoA

Summary for 7P9A

• Entry DOI: 10.2210/pdb7p9a/pdb
• Descriptor: Short-chain acyl-CoA dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, 1,5 Dienoyl-CoA, ... (5 entities in total)
• Functional Keywords: enzyme catalysis, acyl-coa dehydrogenase, oxidoreductase, flavin, fatty acid oxidation
• Biological source: Geobacter metallireducens (strain ATCC 53774 / DSM 7210 / GS-15)
• Total number of polymer chains: 2
• Total formula weight: 92857.44

Authors

Ermler, U.,Weidenweber, S.,Boll, M. (deposition date: 2021-07-26, release date: 2022-07-13, Last modification date: 2024-01-31)

Primary citation

Kung, J.W.,Meier, A.K.,Willistein, M.,Weidenweber, S.,Demmer, U.,Ermler, U.,Boll, M.
Structural Basis of Cyclic 1,3-Diene Forming Acyl-Coenzyme A Dehydrogenases.
Chembiochem, 22:3173-3177, 2021

PubMed Abstract: The biologically important, FAD-containing acyl-coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti-1,2-elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4-elimination at C3 and C6 of cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA) to cyclohex-1,5-diene-1-carboxyl-CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl-CoA. Based on high-resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD-N5 to favor the biologically relevant C3,C6- over the C3,C4-dehydrogenation activity. The C1,C2-dehydrogenation activity was regained by structure-inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3-diene building blocks.

PubMed: 34555236
DOI: 10.1002/cbic.202100421

Experimental method

X-RAY DIFFRACTION (1.5 Å)