Crystal structure of M tuberculosis ABC phosphate transport receptor: specificity and charge compensation dominated by ion-dipole interactions.
The 2.16 A structure of the phosphate-bound PstS-1, the primary extracellular receptor for the ABC phosphate transporter and immunodominant species-specific antigen of Mycobacterium tuberculosis, has been determined. The phosphate, completely engulfed in the cleft between two domains, is bound by 13 hydrogen bonds, 11 of which are formed with NH and OH dipolar donor groups. The further presence of two acidic residues, which serve as acceptors of the protonated phosphate, is key to conferring stringent specificity. The ion-dipole interactions between the phosphate and dipolar groups compensate the ligand's isolated negative charges. Moreover, the surprise finding that the electrostatic surface in and around the cleft is intensely negative demonstrates the power of ion-dipole interactions in anion binding and electrostatic balance. Additional functional features include both the flexible N-terminal segment that tethers PstS-1 on the cell surface and the hinge between the two domains, which should facilitate snaring the phosphate in the medium.
Vyas
Nand K
NK
Verna and Marrs McLean Department, Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Vyas
Meenakshi N
MN
Quiocho
Florante A
FA
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D007477:Ions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D018528:ATP-Binding Cassette Transporters; D007477:Ions