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| | <StructureSection load='5aes' size='340' side='right'caption='[[5aes]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='5aes' size='340' side='right'caption='[[5aes]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5aes]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AES FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5aes]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AES FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5B0:{2-[5-HYDROXY-4-(HYDROXYMETHYL)-6-METHYLPYRIDIN-3-YL]ETHYL}PHOSPHONIC+ACID'>5B0</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5B0:{2-[5-HYDROXY-4-(HYDROXYMETHYL)-6-METHYLPYRIDIN-3-YL]ETHYL}PHOSPHONIC+ACID'>5B0</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyridoxal_phosphatase Pyridoxal phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.74 3.1.3.74] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5aes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aes OCA], [https://pdbe.org/5aes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aes RCSB], [https://www.ebi.ac.uk/pdbsum/5aes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aes ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5aes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aes OCA], [http://pdbe.org/5aes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5aes RCSB], [http://www.ebi.ac.uk/pdbsum/5aes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5aes ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLPP_MOUSE PLPP_MOUSE]] Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho-tyrosine. Pyridoxal phosphate phosphatase. Has some activity towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity with PLP followed by PNP (By similarity). | + | [https://www.uniprot.org/uniprot/PLPP_MOUSE PLPP_MOUSE] Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho-tyrosine. Pyridoxal phosphate phosphatase. Has some activity towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity with PLP followed by PNP (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pyridoxal phosphatase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gohla, A]] | + | [[Category: Gohla A]] |
| - | [[Category: Jabari, N]] | + | [[Category: Jabari N]] |
| - | [[Category: Knobloch, G]] | + | [[Category: Knobloch G]] |
| - | [[Category: Koehn, M]] | + | [[Category: Koehn M]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Schindelin H]] |
| - | [[Category: Had hydrolase]]
| + | |
| - | [[Category: Had phosphatase]]
| + | |
| - | [[Category: Haloacid dehalogenase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Pdxp]]
| + | |
| - | [[Category: Plpp]]
| + | |
| Structural highlights
Function
PLPP_MOUSE Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho-tyrosine. Pyridoxal phosphate phosphatase. Has some activity towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity with PLP followed by PNP (By similarity).
Publication Abstract from PubMed
A set of phosphonic acid derivatives (1-4) of pyridoxal 5'-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79muM, which was in the range of the Km of the physiological substrate PLP. We also report the X-ray crystal structure of PDXP bound to compound 3, which we solved to 2.75A resolution (PDB code 5AES). The co-crystal structure proves that compound 3 binds in the same orientation as PLP, and confirms the mode of inhibition to be competitive. Thus, we identify compound 1 as a PDXP phosphatase inhibitor. Our results suggest a strategy to design new, potent and selective PDXP inhibitors, which may be useful to increase the sensitivity of tumor cells to treatment with cytotoxic agents.
Synthesis of hydrolysis-resistant pyridoxal 5'-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin.,Knobloch G, Jabari N, Stadlbauer S, Schindelin H, Kohn M, Gohla A Bioorg Med Chem. 2015 Mar 4. pii: S0968-0896(15)00153-4. doi:, 10.1016/j.bmc.2015.02.049. PMID:25783190[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Knobloch G, Jabari N, Stadlbauer S, Schindelin H, Kohn M, Gohla A. Synthesis of hydrolysis-resistant pyridoxal 5'-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin. Bioorg Med Chem. 2015 Mar 4. pii: S0968-0896(15)00153-4. doi:, 10.1016/j.bmc.2015.02.049. PMID:25783190 doi:http://dx.doi.org/10.1016/j.bmc.2015.02.049
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