The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein

Background: The surface protein PsaA of the pathogenic bacterium Streptococcus pneumoniae plays an essential role in its virulence. PsaA is a putative ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of Mn2+ and possibly Zn2+ and is considered to be both a potential drug target and and a candidate vaccine component, Results: The structure of PsaA has been determined to 2.0 Angstrom resolution using X-ray crystallography and is the first structure obtained for an ABC-type binding protein from a Gram-positive organism, The protein consists of two (beta/alpha)(4) domains linked together by a single helix. A metal-binding site is formed in the domain interface by the sidechains of His67, His139, Glu205 and Asp280 and is occupied in the structure. Conclusions: The structural topology of PsaA is fundamentally different from that of other ABC-type binding proteins determined thus far in that PsaA lacks the characteristic 'hinge peptides' involved in conformational change upon solute uptake and release, In our structure, the metal-binding Site is probably occupied by Zn2+. The site seems to be well conserved amongst related receptors from both Gram-positive and Gram-negative bacteria.