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Yes—in one reported case, the PhzA/B enzyme from Burkholderia cepacia hosted both mirror-image forms of a racemic ligand in its active site at the same time. The 2009 finding describes an unusual enzyme–ligand interaction, not a general rule for enzymes.
What does it mean to bind both sides of the mirror?
Enantiomers are two forms of a chiral molecule that are mirror images of one another. A racemic mixture contains both forms. In many discussions of binding, the possibilities are that one enantiomer binds while the other does not, or that either can bind separately. The unusual result reported for PhzA/B was different: both enantiomers were present together in the enzyme’s active site.
The finding was reported by Matthias Mentel, Wulf Blankenfeldt, and Rolf Breinbauer in “The Active Site of an Enzyme Can Host Both Enantiomers of a Racemic Ligand Simultaneously,” published in Angewandte Chemie International Edition in 2009. PubMed’s indexed record provides the publication details; the accessible account of the result is in Chemistry World’s report.
What did the study establish?
A specific enzyme–ligand observation
The enzyme was homodimeric PhzA/B, associated with phenazine biosynthesis and studied from Burkholderia cepacia. The reported structural observation was that the two enantiomers arrange differently when present together in the active site. It is evidence about this particular system; it does not show that enzymes generally accommodate both forms at once.
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What the available account does not establish
The accessible sources do not provide the ligand’s identity, crystallographic resolution, occupancy values, or the full experimental protocol. Those details should not be inferred from the headline or treated as established without consulting the full paper. PubMed’s indexed record has no abstract.
Why does simultaneous binding matter?
Racemic mixtures may be used in early screening. If the two enantiomers can bind together and adopt different arrangements, a screening result may be more complicated than the assumption that one form is active and the other inert. The report raises the possibility of cooperative effects, but does not establish them as a general rule or demonstrate a clinical outcome.
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Rolf Breinbauer summarized the broader lesson in the Chemistry World account: “Our findings show that the world is more complicated.” The practical implication is caution in interpreting binding data from a racemic mixture, rather than a reason to assume that co-binding will occur in other enzymes.
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Could this guide drug discovery?
Dafydd Owen of Pfizer Research Chemistry suggested a possible fragment-based discovery idea: use structural features from the two bound forms to inspire a hybrid molecule. That was a proposed design angle, not a report that a hybrid drug candidate was made, validated, or shown to work therapeutically.
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Owen’s caution for interpreting experiments was: “People need to consider more options when interpreting binding data from racemic mixtures.” For a researcher, the key distinction is among one enantiomer binding, either enantiomer binding in separate instances, and both binding simultaneously. The PhzA/B report describes the third case.
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