1nd5

Crystal Structures of Human Prostatic Acid Phosphatase in Complex with a Phosphate Ion and alpha-Benzylaminobenzylphosphonic Acid Update the Mechanistic Picture and Offer New Insights into Inhibitor Design

spinqualitylabelsall models 1nd5, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1nd5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: 1PE, 2BF, MAN, NAG, NDG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPAP_HUMAN A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma. Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The X-ray crystal structure of human prostatic acid phosphatase (PAP) in complex with a phosphate ion has been determined at 2.4 A resolution. This structure offers a snapshot of the final intermediate in the catalytic mechanism and does not support the role of Asp 258 as a proton donor in catalysis. A total of eight hydrogen bonds serve to strongly bind the phosphate ion within the active site. Bound PEG molecules from the crystallization matrix have allowed the identification of a channel within the molecule that likely plays a role in molecular recognition and in macromolecular substrate selectivity. Additionally, the structure of PAP in complex with a phosphate derivative, alpha-benzylaminobenzylphosphonic acid, a potent inhibitor (IC(50) = 4 nM), has been determined to 2.9 A resolution. This structure gives new insight into the determinants of binding hydrophobic ligands within the active site and allows us to explain PAP's preference for aromatic substrates. Crystal structures of human prostatic acid phosphatase in complex with a phosphate ion and alpha-benzylaminobenzylphosphonic acid update the mechanistic picture and offer new insights into inhibitor design.,Ortlund E, LaCount MW, Lebioda L Biochemistry. 2003 Jan 21;42(2):383-9. PMID:12525165 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acid phosphatase 3D structures

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