Crystal structure of a mammalian purple acid phosphatase.
Tartrate-resistant acid phosphatase (TRAP) is a mammalian di-iron- containing enzyme that belongs to the family of purple acid phosphatases (PAP). It is highly expressed in a limited number of tissues, predominantly in bone-resorbing osteoclasts and in macrophages of spleen. We have determined the crystal structure of rat TRAP in complex with a phosphate ion to 2.7 A resolution. The fold resembles that of the catalytic domain of kidney bean purple acid phosphatase (KBPAP), although the sequence similarity is limited to the active site residues. A surface loop near the active site is absent due to proteolysis, leaving the active-site easily accessible from the surrounding solvent. This, we believe, gives a structural explanation for the observed proteolytic activation of TRAP. The current structure was determined at a relatively high pH and without any external reducing agents. It is likely that it represents an oxidized and therefore catalytically inactive form of the enzyme.
Uppenberg
J
J
Department of Structural Chemistry, Pharmacia and Upjohn, Lindhagensgatan 133, Stockholm, S-112 87, Sweden. jonas.uppenberg@eu.pnu.com
Lindqvist
F
F
Svensson
C
C
Ek-Rylander
B
B
Andersson
G
G
D000135:Acid Phosphatase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017386:Sequence Homology, Amino Acid
D006023:Glycoproteins; C091137:purple acid phosphatase; D000135:Acid Phosphatase