1ew2
From Proteopedia
(New page: 200px<br /> <applet load="1ew2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ew2, resolution 1.82Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1ew2.gif|left|200px]]<br /> | + | [[Image:1ew2.gif|left|200px]]<br /><applet load="1ew2" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ew2" size=" | + | |
caption="1ew2, resolution 1.82Å" /> | caption="1ew2, resolution 1.82Å" /> | ||
'''CRYSTAL STRUCTURE OF A HUMAN PHOSPHATASE'''<br /> | '''CRYSTAL STRUCTURE OF A HUMAN PHOSPHATASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human placental alkaline phosphatase (PLAP) is one of three | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EW2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, ZN, MG and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1EW2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EW2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Du, M | + | [[Category: Du, M H.Le.]] |
[[Category: Menez, A.]] | [[Category: Menez, A.]] | ||
[[Category: Stigbrand, T.]] | [[Category: Stigbrand, T.]] | ||
| - | [[Category: Stura, E | + | [[Category: Stura, E A.]] |
| - | [[Category: Taussig, M | + | [[Category: Taussig, M J.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: phosphatase]] | [[Category: phosphatase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:32:06 2008'' |
Revision as of 10:32, 21 February 2008
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CRYSTAL STRUCTURE OF A HUMAN PHOSPHATASE
Contents |
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 , , and 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 Thu Feb 21 12:32:06 2008
Categories: Alkaline phosphatase | Homo sapiens | Single protein | Du, M H.Le. | Menez, A. | Stigbrand, T. | Stura, E A. | Taussig, M J. | MG | NAG | PO4 | ZN | Non covalent complex | Phosphatase
