Crystal structure of mammalian purple acid phosphatase

Abstract

Despite less than 15% sequence identity, the protein fold resembles that of the catalytic domain of plant purple acid phosphatase and some serine/threonine protein phosphatases. The active-site regions of the mammalian and plant purple acid phosphatases differ significantly, however. The internal symmetry suggests that the binuclear centre evolved as a result of the combination of mononuclear ancestors. The structure of the mammalian enzyme provides a basis for antiosteoporotic drug design.

Structure, function, and regulation of tartrate-resistant acid phosphatase

“…66 Sequence alignment of RKBPAP with porcine TRAP suggested that RKBPAP is a good model for the structure and mechanism of other acid phosphatases. 67 We recently confirmed this overall prediction with solution of the crystal structure of the porcine enzyme at 1.5 Å resolution 39 (Brookhaven Database, Access Code 1ute). Together with other groups we produced substantial amounts of recombinant mouse, rat, and human TRAP in baculovirus expression systems.…”

Phosphotyrosyl peptides and analogues as substrates and inhibitors of purple acid phosphatases

“…We have determined the crystal structure of pig purple acid phosphatase [23] and other groups have solved the structures of the rat enzyme [42,43]. The overall structural features of these mammalian enzymes are very similar, as expected based on the very high degree of sequence identity (>85%) [1].…”

“…The pK es2 value of $6 may correspond to a residue in the active site acting as a general acid to protonate the leaving group on hydrolysis. Residues previously identified as candidates, based on the crystal structures of the pig and red kidney bean enzymes, are the conserved His92 and His195 (pig enzyme numbering), which are within hydrogen bonding distance of bound phosphate [23,32].…”

“…Protons were added to the 1.55 A resolution crystal structure of the pig enzyme (1UTE in the protein data bank [23]) using BIOPOLYMER, a module of INSIGHT 2000.1 (Accelrys). For this process, it was assumed that the protein was at pH 3.5.…”

Direct Electrochemistry of Porcine Purple Acid Phosphatase (Uteroferrin)

“…Crystal structures have been reported for PAPs isolated from pig uterus, also known as uteroferrin or Uf ( Figure 1) (14), rat bone (15), and red kidney bean (16,17). All PAPs bear an active site comprising a ferric ion (site A) and a divalent metal ion (site B).…”