1zed: Difference between revisions
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|PDB= 1zed |SIZE=350|CAPTION= <scene name='initialview01'>1zed</scene>, resolution 1.57Å | |PDB= 1zed |SIZE=350|CAPTION= <scene name='initialview01'>1zed</scene>, resolution 1.57Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PNP:METHYL-PHOSPHONIC+ACID+MONO-(4-NITRO-PHENYL)+ESTER'>PNP</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1ew2|1EW2]], [[1zeb|1ZEB]], [[1zef|1ZEF]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zed FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zed OCA], [http://www.ebi.ac.uk/pdbsum/1zed PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zed RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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== | ==About this Structure== | ||
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[[Category: Stigbrand, T.]] | [[Category: Stigbrand, T.]] | ||
[[Category: Stura, E A.]] | [[Category: Stura, E A.]] | ||
[[Category: alkaline phosphatase]] | [[Category: alkaline phosphatase]] | ||
[[Category: phosphoserine]] | [[Category: phosphoserine]] | ||
[[Category: substrate analog]] | [[Category: substrate analog]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:34:48 2008'' | ||
Revision as of 01:34, 31 March 2008
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| , resolution 1.57Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , | ||||||
| Activity: | Alkaline phosphatase, with EC number 3.1.3.1 | ||||||
| Related: | 1EW2, 1ZEB, 1ZEF
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Alkaline phosphatase from human placenta in complex with p-nitrophenyl-phosphonate
OverviewOverview
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 StructureAbout this Structure
1ZED is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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