1ew2

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1ew2, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF A HUMAN PHOSPHATASE

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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 Millan, 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.

Disease

Known disease associated with this structure: Osteoarthritis, susceptibility to OMIM:[608135]

About this Structure

1EW2 is a Single protein structure of sequence from Homo sapiens with NAG, ZN, MG and PO4 as ligands. Active as Alkaline phosphatase, with EC number 3.1.3.1 Full crystallographic information is available from OCA.

Reference

Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity., Le Du MH, Stigbrand T, Taussig MJ, Menez A, Stura EA, J Biol Chem. 2001 Mar 23;276(12):9158-65. Epub 2000 Dec 20. PMID:11124260

Page seeded by OCA on Mon Nov 12 16:47:09 2007