2YJP

Crystal structure of the solute receptors for L-cysteine of Neisseria gonorrhoeae

Summary for 2YJP

• Entry DOI: 10.2210/pdb2yjp/pdb
• Related: 2YLN 3ZSF
• Descriptor: PUTATIVE ABC TRANSPORTER, PERIPLASMIC BINDING PROTEIN, AMINO ACID, CYSTEINE, ZINC ION, ... (5 entities in total)
• Functional Keywords: transport protein, solute-binding protein
• Biological source: NEISSERIA GONORRHOEAE
• Total number of polymer chains: 3
• Total formula weight: 95469.28

Authors

Bulut, H.,Moniot, S.,Scheffel, F.,Gathmann, S.,Licht, A.,Saenger, W.,Schneider, E. (deposition date: 2011-05-23, release date: 2011-12-14, Last modification date: 2023-12-20)

Primary citation

Bulut, H.,Moniot, S.,Licht, A.,Scheffel, F.,Gathmann, S.,Saenger, W.,Schneider, E.
Crystal Structures of Two Solute Receptors for L-Cystine and L-Cysteine, Respectively, of the Human Pathogen Neisseria Gonorrhoeae.
J.Mol.Biol., 415:560-, 2012

PubMed Abstract: ATP-binding cassette (ABC) transporters are integral membrane proteins that carry a variety of substrates across biological membranes at the expense of ATP. The here considered prokaryotic canonical importers consist of three entities: an extracellular solute receptor, two membrane-intrinsic proteins forming a translocation pathway, and two cytoplasmic ATP-binding subunits. The ngo0372-74 and ngo2011-14 gene clusters from the human pathogen Neisseria gonorrhoeae were predicted by sequence homology as ABC transporters for the uptake of cystine and cysteine, respectively, and chosen for structural characterization. The structure of the receptor component Ngo0372 was obtained in a ligand-free "open" conformation and in a "closed" conformation when co-crystallized with L-cystine. Our data provide the first structural information of an L-cystine ABC transporter. Dissociation constants of 21 and 33 nM for L-cystine and L-selenocystine, respectively, were determined by isothermal titration calorimetry. In contrast, L-cystathionine and L-djenkolic acid are weak binders, while no binding was detectable for S-methyl-L-cysteine. Mutational analysis of two residues from the binding pocket, Trp97 and Tyr59, revealed that the latter is crucial for L-cystine binding. The structure of the Ngo2014 receptor was obtained in closed conformation in complex with co-purified L-cysteine. The protein binds L-cysteine with a K(d) of 26 nM. Comparison of the structures of both receptors and analysis of the ligand binding sites shed light on the mode of ligand recognition and provides insight into the tight binding of both substrates. Moreover, since L-cystine limitation leads to reduction in virulence of N. gonorrhoeae, Ngo0372 might be suited as target for an antimicrobial vaccine.

PubMed: 22138345
DOI: 10.1016/J.JMB.2011.11.030

Experimental method

X-RAY DIFFRACTION (2.26 Å)