4z9b: Difference between revisions
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==Crystal structure of Low Molecular Weight Protein Tyrosine Phosphatase isoform A complexed with benzylphosphonic acid== | ==Crystal structure of Low Molecular Weight Protein Tyrosine Phosphatase isoform A complexed with benzylphosphonic acid== | ||
<StructureSection load='4z9b' size='340' side='right' caption='[[4z9b]], [[Resolution|resolution]] 2.41Å' scene=''> | <StructureSection load='4z9b' size='340' side='right'caption='[[4z9b]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4z9b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9B OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4z9b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z9B FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.41Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B85:BENZYLPHOSPHONIC+ACID'>B85</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4z9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z9b OCA], [https://pdbe.org/4z9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z9b RCSB], [https://www.ebi.ac.uk/pdbsum/4z9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z9b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PPAC_HUMAN PPAC_HUMAN] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Tyrosine phosphatase|Tyrosine phosphatase]] | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Aparicio R]] | ||
[[Category: | [[Category: Dias MP]] | ||
[[Category: | [[Category: Fonseca EMB]] | ||
[[Category: | [[Category: Miranda PCML]] | ||
[[Category: | [[Category: Scorsato V]] | ||
[[Category: | [[Category: Trivella DBB]] | ||
[[Category: | [[Category: De Oliveira FL]] | ||
Latest revision as of 11:14, 27 September 2023
Crystal structure of Low Molecular Weight Protein Tyrosine Phosphatase isoform A complexed with benzylphosphonic acidCrystal structure of Low Molecular Weight Protein Tyrosine Phosphatase isoform A complexed with benzylphosphonic acid
Structural highlights
FunctionPPAC_HUMAN Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity. Publication Abstract from PubMedLow molecular weight protein tyrosine phosphatases (LMW-PTP, EC 3.1.3.48) are a family of single-domain enzymes with molecular weight up to 18kDa, expressed in different tissues and considered attractive pharmacological targets for cancer chemotherapy. Despite this, few LMW-PTP inhibitors have been described to date, and the structural information on LMW-PTP druggable binding sites is scarce. In this study, a small series of phosphonic acids were designed based on a new crystallographic structure of LMW-PTP complexed with benzylsulfonic acid, determined at 2.1A. In silico docking was used as a tool to interpret the structural and enzyme kinetics data, as well as to design new analogs. From the synthesized series, two compounds were found to act as competitive inhibitors, with inhibition constants of 0.124 and 0.047mM. We also report the 2.4A structure of another complex in which LMW-PTP is bound to benzylphosphonic acid, and a structure of apo LMW-PTP determined at 2.3A resolution. Although no appreciable conformation changes were observed, in the latter structures, amino acid residues from an expression tag were found bound to a hydrophobic region at the protein surface. This regions is neighbored by positively charged residues, adjacent to the active site pocket, suggesting that this region might be not a mere artefact of crystal contacts but an indication of a possible anchoring region for the natural substrate-which is a phosphorylated protein. Crystal structures of the apo form and a complex of human LMW-PTP with a phosphonic acid provide new evidence of a secondary site potentially related to the anchorage of natural substrates.,Fonseca EM, Trivella DB, Scorsato V, Dias MP, Bazzo NL, Mandapati KR, de Oliveira FL, Ferreira-Halder CV, Pilli RA, Miranda PC, Aparicio R Bioorg Med Chem. 2015 Jun 14. pii: S0968-0896(15)00511-8. doi:, 10.1016/j.bmc.2015.06.017. PMID:26117648[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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