Crystal structure of enoyl‐CoA hydratase from Thermus thermophilus HB8

다국어 초록 (Multilingual Abstract)

Fatty‐acid degradation is an oxidative process that involves four enzymatic steps and is referred to as the β‐oxidation pathway. During this process, long‐chain acyl‐CoAs are broken down into acetyl‐CoA, which enters the mitochondrial tricarboxylic acid (TCA) cycle, resulting in the production of energy in the form of ATP. Enoyl‐CoA hydratase (ECH) catalyzes the second step of the β‐oxidation pathway by the syn addition of water to the double bond between C2 and C3 of a 2‐trans‐enoyl‐CoA, resulting in the formation of a 3‐hydroxyacyl CoA. Here, the crystal structure of ECH from Thermus thermophilus HB8 (TtECH) is reported at 2.85 Å resolution. TtECH forms a hexamer as a dimer of trimers, and wide clefts are uniquely formed between the two trimers. Although the overall structure of TtECH is similar to that of a hexameric ECH from Rattus norvegicus (RnECH), there is a significant shift in the positions of the helices and loops around the active‐site region, which includes the replacement of a longer α3 helix with a shorter α‐helix and 310‐helix in RnECH. Additionally, one of the catalytic residues of RnECH, Glu144 (numbering based on the RnECH enzyme), is replaced by a glycine in TtECH, while the other catalytic residue Glu164, as well as Ala98 and Gly141 that stabilize the enolate intermediate, is conserved. Their putative ligand‐binding sites and active‐site residue compositions are dissimilar.
Enoyl‐CoA hydratase (ECH) catalyzes the second step of the β‐oxidation pathway. Here, the crystal structure of ECH from T. thermophilus HB8 is reported at 2.85 Å resolution.