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 A 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.
Lawrence
M C
MC
Biomolecular Research Institute 343 Royal Parade Parkville Victoria 3052 Australia. mike.lawrence@bioresi.com.au
Pilling
P A
PA
Epa
V C
VC
Berry
A M
AM
Ogunniyi
A D
AD
Paton
J C
JC
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins; D018360:Crystallography, X-Ray; D008074:Lipoproteins; D008345:Manganese / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; C085000:PsaA protein, Streptococcus; D008345:Manganese; D015032:Zinc