1zed
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1zed.gif|left|200px]] | [[Image:1zed.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1zed", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1zed| PDB=1zed | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Alkaline phosphatase from human placenta in complex with p-nitrophenyl-phosphonate''' | '''Alkaline phosphatase from human placenta in complex with p-nitrophenyl-phosphonate''' | ||
| Line 33: | Line 30: | ||
[[Category: Stigbrand, T.]] | [[Category: Stigbrand, T.]] | ||
[[Category: Stura, E A.]] | [[Category: Stura, E A.]] | ||
| - | [[Category: | + | [[Category: Alkaline phosphatase]] |
| - | [[Category: | + | [[Category: Phosphoserine]] |
| - | [[Category: | + | [[Category: Substrate analog]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:31:20 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:31, 3 May 2008
Alkaline phosphatase from human placenta in complex with p-nitrophenyl-phosphonate
Overview
The activity of human placental alkaline phosphatase (PLAP) is downregulated by a number of effectors such as l-phenylalanine, an uncompetitive inhibitor, 5'-AMP, an antagonist of the effects of PLAP on fibroblast proliferation and by p-nitrophenyl-phosphonate (PNPPate), a non-hydrolysable substrate analogue. For the first two, such regulation may be linked to its biological function that requires a reduced and better-regulated hydrolytic rate. To understand how such disparate ligands are able to inhibit the enzyme, we solved the structure of the complexes at 1.6A, 1.9A and 1.9A resolution, respectively. These crystal structures are the first of an alkaline phosphatase in complex with organic inhibitors. Of the three inhibitors, only l-Phe and PNPPate bind at the active site hydrophobic pocket, providing structural data on the uncompetitive inhibition process. In contrast, all three ligands interact at a remote peripheral site located 28A from the active site. In order to extend these observations to the other members of the human alkaline phosphatase family, we have modelled the structures of the other human isozymes and compared them to PLAP. This comparison highlights the crucial role played by position 429 at the active site in the modulation of the catalytic process, and suggests that the peripheral binding site may be involved in the functional specialization of the PLAP isozyme.
About this Structure
1ZED is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural studies of human placental alkaline phosphatase in complex with functional ligands., Llinas P, Stura EA, Menez A, Kiss Z, Stigbrand T, Millan JL, Le Du MH, J Mol Biol. 2005 Jul 15;350(3):441-51. PMID:15946677 Page seeded by OCA on Sat May 3 17:31:20 2008
