Structure of Francisella tularensis AcpA: prototype of a unique superfamily of acid phosphatases and phospholipases C.
AcpA is a respiratory burst-inhibiting acid phosphatase from the Centers for Disease Control and Prevention Category A bioterrorism agent Francisella tularensis and prototype of a superfamily of acid phosphatases and phospholipases C. We report the 1.75-A resolution crystal structure of AcpA complexed with the inhibitor orthovanadate, which is the first structure of any F. tularensis protein and the first for any member of this superfamily. The core domain is a twisted 8-stranded beta-sheet flanked by three alpha-helices on either side, with the active site located above the carboxyl-terminal edge of the beta-sheet. This architecture is unique among acid phosphatases and resembles that of alkaline phosphatase. Unexpectedly, the active site features a serine nucleophile and metal ion with octahedral coordination. Structure-based sequence analysis of the AcpA superfamily predicts that the hydroxyl nucleophile and metal center are also present in AcpA-like phospholipases C. These results imply a phospholipase C catalytic mechanism that is radically different from that of zinc metallophospholipases.
Felts
Richard L
RL
Department of Chemistry, University of Missouri, Columbia, Missouri 65211, USA.
Reilly
Thomas J
TJ
Tanner
John J
JJ
D000135:Acid Phosphatase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D005604:Francisella tularensis / Q000201:enzymology* / Q000235:genetics; D008667:Metalloproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016415:Sequence Alignment; D010738:Type C Phospholipases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014638:Vanadates / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
D001426:Bacterial Proteins; D008667:Metalloproteins; D014638:Vanadates; D000135:Acid Phosphatase; D010738:Type C Phospholipases; D015032:Zinc