Structural insights into the catalytic mechanism of the bacterial class B phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases.
AphA is a magnesium-dependent, bacterial class B acid phosphatase that catalyzes the hydrolysis of a variety of phosphoester substrates and belongs to the DDDD superfamily of phosphohydrolases. The recently reported crystal structure of AphA from Escherichia coli has revealed the quaternary structure of the enzyme together with hints about its catalytic mechanism. The present work reports the crystal structures of AphA from E. coli in complex with substrate, transition-state, and intermediate analogues. The structures provide new insights into the mechanism of the enzyme and allow a revision of some aspects of the previously proposed mechanism that have broader implications for all the phosphatases of the DDDD superfamily.
Dipartimento di Chimica, Università di Siena, Via Aldo Moro 2, I-53100 Siena, Italy.
Rosalida
R
Leone
Emilia
E
Cappelletti
Manuela
M
Benvenuti
Gianluca
G
Lentini
Maria Cristina
MC
Thaller
Stefano
S
Mangani
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D017607:Aluminum Compounds / Q000737:chemistry; D000814:Aniline Compounds / Q000378:metabolism; D001608:Beryllium / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D005459:Fluorides / Q000737:chemistry; D006860:Hydrogen Bonding / Q000187:drug effects; D005810:Multigene Family; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000378:metabolism; D017433:Protein Structure, Secondary; D013379:Substrate Specificity / Q000187:drug effects
D017607:Aluminum Compounds; D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C035982:beryllium fluoride; C053001:adefovir; C068798:4-aminophenylphosphate; D000135:Acid Phosphatase; C508128:AphA protein, E coli; D000225:Adenine; D001608:Beryllium; D005459:Fluorides; C032311:aluminum fluoride