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PDBsum entry 1ew2

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Hydrolase PDB id
1ew2
Jmol
Contents
Protein chain
479 a.a. *
Ligands
NAG
PO4
Metals
_ZN ×2
_MG ×2
Waters ×602
* Residue conservation analysis

References listed in PDB file
Key reference
Title Crystal structure of alkaline phosphatase from human placenta at 1.8 a resolution. Implication for a substrate specificity.
Authors M.H.Le du, T.Stigbrand, M.J.Taussig, A.Menez, E.A.Stura.
Ref. J Biol Chem, 2001, 276, 9158-9165. [DOI no: 10.1074/jbc.M009250200]
PubMed id 11124260
Abstract
Human placental alkaline phosphatase (PLAP) is one of three tissue-specific human APs extensively studied because of its ectopic expression in tumors. The crystal structure, determined at 1.8-A resolution, reveals that during evolution, only the overall features of the enzyme have been conserved with respect to Escherichia coli. The surface is deeply mutated with 8% residues in common, and in the active site, only residues strictly necessary to perform the catalysis have been preserved. Additional structural elements aid an understanding of the allosteric property that is specific for the mammalian enzyme (Hoylaerts, M. F., Manes, T., and Millán, J. L. (1997) J. Biol. Chem. 272, 22781-22787). Allostery is probably favored by the quality of the dimer interface, by a long N-terminal alpha-helix from one monomer that embraces the other one, and similarly by the exchange of a residue from one monomer in the active site of the other. In the neighborhood of the catalytic serine, the orientation of Glu-429, a residue unique to PLAP, and the presence of a hydrophobic pocket close to the phosphate product, account for the specific uncompetitive inhibition of PLAP by l-amino acids, consistent with the acquisition of substrate specificity. The location of the active site at the bottom of a large valley flanked by an interfacial crown-shaped domain and a domain containing an extra metal ion on the other side suggest that the substrate of PLAP could be a specific phosphorylated protein.
Figure 1.
Fig. 1. Electron density for carbohydrates and fourth metal ion. a and b, glycosylation site connected to Asn-122 corresponding, respectively, to the reported 1.8-Å structure (a) and to a 2.1-Å data set still under refinement (b) (Table I). c, carbohydrate connected to Asn-249 in stacking with Trp-248 and coordination of the fourth metal ion with Glu-216, Phe-269-CO, Glu-270-O 2, Asp-285, and one water molecule. In each case, the 2 F[o] F[c] map is shown in blue and is contoured at the 1.2 level. The F[o] F[c] map is shown in green and contoured at 10 level. This figure was made with TURBO (34).
Figure 5.
Fig. 5. Uncompetitive inhibition. Shown is modeling of L-Phe uncompetitive inhibitor in the active site of PLAP. The L-Phe amino acid is in stick representation colored in yellow. PLAP is in Corey-Pauling-Koltun representation with one monomer colored in white and the second colored in pink. Residues of PLAP interacting with L-Phe are colored in residue type: acidic in red, basic in blue, neutral in green, aromatic in violet. The metal ions are colored in orange. This figure was made with TURBO.
The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 9158-9165) copyright 2001.
PROCHECK
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