3M8U

Crystal structure of glutathione-binding protein A (GbpA) from Haemophilus parasuis SH0165 in complex with glutathione disulfide (GSSG)

Summary for 3M8U

• Entry DOI: 10.2210/pdb3m8u/pdb
• Descriptor: Heme-binding protein A, OXIDIZED GLUTATHIONE DISULFIDE, MALONATE ION, ... (4 entities in total)
• Functional Keywords: glutathione binding protein, abc-type transport system, periplasmic component, transport protein
• Biological source: Haemophilus parasuis
• Total number of polymer chains: 1
• Total formula weight: 59570.59

Authors

Vergauwen, B.,Elegheert, J.,Dansercoer, A.,Devreese, B.,Savvides, S.N. (deposition date: 2010-03-19, release date: 2010-07-14, Last modification date: 2024-11-13)

Primary citation

Vergauwen, B.,Elegheert, J.,Dansercoer, A.,Devreese, B.,Savvides, S.N.
Glutathione import in Haemophilus influenzae Rd is primed by the periplasmic heme-binding protein HbpA
Proc.Natl.Acad.Sci.USA, 107:13270-13275, 2010

PubMed Abstract: Glutathione (GSH) is a vital intracellular cysteine-containing tripeptide across all kingdoms of life and assumes a plethora of cellular roles. Such pleiotropic behavior relies on a finely tuned spatiotemporal distribution of glutathione and its conjugates, which is not only controlled by synthesis and breakdown, but also by transport. Here, we show that import of glutathione in the obligate human pathogen Haemophilus influenzae, a glutathione auxotrophe, is mediated by the ATP-binding cassette (ABC)-like dipeptide transporter DppBCDF, which is primed for glutathione transport by a dedicated periplasmic-binding protein (PBP). We have identified the periplasmic lipoprotein HbpA, a protein hitherto implicated in heme acquisition, as the cognate PBP that specifically binds reduced (GSH) and oxidized glutathione (GSSG) forms of glutathione with physiologically relevant affinity, while it exhibits marginal binding to hemin. Dissection of the ligand preferences of HbpA showed that HbpA does not recognize bulky glutathione S conjugates or glutathione derivatives with C-terminal modifications, consistent with the need for selective import of useful forms of glutathione and the concomitant exclusion of potentially toxic glutathione adducts. Structural studies of the highly homologous HbpA from Haemophilus parasuis in complex with GSSG have revealed the structural basis of the proposed novel function for HbpA-like proteins, thus allowing a delineation of highly conserved structure-sequence fingerprints for the entire family of HbpA proteins. Taken together, our studies unmask the main physiological role of HbpA and establish a paradigm for glutathione import in bacteria. Accordingly, we propose a name change for HbpA to glutathione-binding protein A.

PubMed: 20628015
DOI: 10.1073/pnas.1005198107

Experimental method

X-RAY DIFFRACTION (1.85 Å)