Structural and functional insights of itaconyl ‐CoA hydratase from Pseudomonas aeruginosa highlight a novel N‐terminal hotdog fold

Here, we report the first crystal structure ofPaIch at 1.98  Å resolution. A unique N-terminal hotdog fold containing a short helical segment α3-, named an “eaten sausage”, slipped away from the conserved β-sheet scaffold, whereas central helices of other N- as well as C-terminal hotdog fold containing hydratases are properly wrapped up by their res pective β-sheet scaffold. Itaconyl-CoA hydratase inPseudomonas aeruginosa (PaIch) converts itaconyl-CoA to (S)-citramalyl-CoA upon addition of a water molecule, a part of an itaconate catabolic pathway in virulent organisms required for their survival in humans host cells. Crystal structure analysis ofPaIch showed that a unique N-terminal hotdog fold containing a 4-residue short helical segment α3-, named as an “eaten sausage”, followed by a flexible loop region slipped away from the conserved β-sheet scaffold, whereas the C-terminal hotdog fold is similar to all MaoC. A conserved hydratase motif with catalytic residues provides mechanistic insights into catalysis, and existence of a longer substrate binding tunnel may suggest the binding of longer CoA derivatives.

Source: FEBS Letters - April 5, 2024 Category: Biochemistry Authors: Atanu Pramanik, Saumen Datta Tags: Research Article Source Type: research