Extended Data Fig. 3: Crystal structure and phylogenetic analysis of the iminosuccinate reductase BhcD.

a, Cartoon representation of the iminosuccinate reductase homodimer (PDB 6RQA) with superimposed protein surface (left, side view; right, top view). b, Active site of BhcD with bound NAD⁺ (light cyan). Residues highlighted in pink (V39, R41, G52, K54 and H83) may contribute to substrate binding and are conserved among iminosuccinate reductases, but differ in l-alanine dehydrogenases. c, Active site of l-alanine dehydrogenase (PDB 1OMO). The corresponding conserved residues among l-alanine dehydrogenases (K41, Y43, R52, M54 and V81) are highlighted as in b. d, Maximum likelihood phylogenetic tree of the ornithine cyclodeaminase/µ-crystalline protein superfamily. Sequences of the iminosuccinate reductase BhcD and its homologues form a distinct clade (red) within this superfamily. Bootstrap values of at least 50 are given on the respective nodes. e, Sequence similarity network of 1,614 sequences from the ornithine cyclodeaminase/µ-crystalline protein superfamily. Connected sequences with more than 80% identity are clustered into nodes. The number in each node gives the number of sequences contained within. Nodes with more than 50% identity are connected by edges. Similar to the phylogenetic analysis shown in d, sequences of the iminosuccinate reductase BhcD and its homologues form a distinct clade (red) within this superfamily.