24gf | pdb_000024gf
Crystal structure of HpsK from Ruegeria pomeroyi in complex with R-DHPS (2,3-dihydroxypropanesulfonate)
Structural highlights
Publication Abstract from PubMedBacterial catabolism of 2,3-dihydroxypropanesulfonate (DHPS) links algal production to marine degradation and connects sulfosugar metabolism to sulfide production in the gut. In surface seawater, DHPS occurs as a dilute, mixed R/S pool, whereas in the anaerobic gut it is produced predominantly as S-DHPS through bacterial sulfoglycolysis pathways. Uptake is achieved via tripartite ATP-independent periplasmic (TRAP) transporters that employ periplasmic substrate-binding proteins (HpsK), but the molecular basis of enantiomer recognition has not been defined. Here, we compare HpsK proteins from the marine bacterium Ruegeria pomeroyi and the gut anaerobe Bilophila wadsworthia using proteomics, biophysical analysis, X-ray crystallography, and bioinformatics. RpHpsK binds both R- and S-DHPS with low-nanomolar affinity (K (D) 5-9 nM), whereas BwHpsK binds selectively to S-DHPS (K (D) 530 nM), representing an approximately 100-fold difference in affinity and strict stereoselectivity. Crystal structures reveal two contrasting strategies for chiral recognition: RpHpsK accommodates both enantiomers through subtle side-chain "toggling" within an otherwise conserved binding pocket, whereas BwHpsK achieves stereoselectivity through a distinct hydrogen-bonding network and a binding site that sterically excludes R-DHPS. Sequence similarity and genome neighbourhood analyses place these proteins in separate clusters associated with oxidative (HpsNOP) or glycyl radical enzyme-linked (HpsGH/HpfGH) pathways. These findings show how changes in binding-site architecture tune ligand stereoselectivity and illustrate the adaptation of TRAP-associated substrate binding proteins to distinct ecological and metabolic niches. Chiral recognition of 2,3-dihydroxypropanesulfonate by bacterial transport proteins adapted to distinct ecological niches.,Barber H, Borusak S, Stewart AWE, Tahir H, Scott NE, Schleheck D, Lee M, Williams SJ Chem Sci. 2026 Jun 19;17(32):15566-15579. doi: 10.1039/d6sc02372j. eCollection , 2026 Aug 19. PMID:42441157[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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