Abstract
Lactate racemase is a microbial enzyme that interconverts the
d
‐ and
l
‐isomers of lactic acid. The enzyme contains a covalently bound nickel cofactor that includes a modified nicotinic acid mononucleotide. The carboxyl group on the pyridinium ring is linked to a protein lysine residue but with sulfur incorporated to form a thioamide rather than amide bond. The pyridinium ring is further modified by appending a thioacid at the C5 position. Nickel is coordinated in near planar geometry by the thioamide sulfur, C4 of the pyridinium ring, the sulfur of the thioacid, and an additional histidine side chain. The lactate racemase cofactor thus represents an (SCS)Ni(II) pincer complex, the first example of an organometallic pincer complex found in a biological context. The cofactor is likely to be a hydride acceptor during transient formation of a pyruvate intermediate, which is reduced from either face to achieve racemization.
Ribbon representation of lactate racemase from
Lactobacillus plantarum
(PDB code: 5HUQ). The active site is identified by the bound cofactor and its nickel ion. If not stated otherwise, figures in this article were created using UCSF Chimera,
1
coloring oxygen, nitrogen, sulfur, phosphorus, and nickel atoms as red, blue, yellow, orange, and green, respectively. The nickel coordination is represented by green dotted lines. The carbon atoms of the cofactor are always illustrated in cyan, while protein carbon atoms are shown in the same color as the ribbon representation.