5iu6: Difference between revisions
New page: '''Unreleased structure''' The entry 5iu6 is ON HOLD until Mar 17 2018 Authors: Timofeev, V.I., Abramchik, Y.A., Esipov, R.S., Kuranova, I.P. Description: Crystal structure of E.coli p... |
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The | ==Crystal structure of E.coli purine nucleoside phosphorylase with 7-deazahypoxanthine== | ||
<StructureSection load='5iu6' size='340' side='right'caption='[[5iu6]], [[Resolution|resolution]] 2.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5iu6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IU6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.51Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7HX:7H-PYRROLO[2,3-D]PYRIMIDIN-4-OL'>7HX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5iu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu6 OCA], [https://pdbe.org/5iu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iu6 RCSB], [https://www.ebi.ac.uk/pdbsum/5iu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DEOD_ECOLI DEOD_ECOLI] Cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules.[HAMAP-Rule:MF_01627] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Purine nucleoside phosphorylases (EC 2.4.2.1; PNPs) reversibly catalyze the phosphorolytic cleavage of glycosidic bonds in purine nucleosides to generate ribose 1-phosphate and a free purine base, and are key enzymes in the salvage pathway of purine biosynthesis. They also catalyze the transfer of pentosyl groups between purine bases (the transglycosylation reaction) and are widely used for the synthesis of biologically important analogues of natural nucleosides, including a number of anticancer and antiviral drugs. Potent inhibitors of PNPs are used in chemotherapeutic applications. The detailed study of the binding of purine bases and their derivatives in the active site of PNPs is of particular interest in order to understand the mechanism of enzyme action and for the development of new enzyme inhibitors. Here, it is shown that 7-deazahypoxanthine (7DHX) is a noncompetitive inhibitor of the phosphorolysis of inosine by recombinant Escherichia coli PNP (EcPNP) with an inhibition constant Ki of 0.13 mM. A crystal of EcPNP in complex with 7DHX was obtained in microgravity by the counter-diffusion technique and the three-dimensional structure of the EcPNP-7DHX complex was solved by molecular replacement at 2.51 A resolution using an X-ray data set collected at the SPring-8 synchrotron-radiation facility, Japan. The crystals belonged to space group P6122, with unit-cell parameters a = b = 120.370, c = 238.971 A, and contained three subunits of the hexameric enzyme molecule in the asymmetric unit. The 7DHX molecule was located with full occupancy in the active site of each of the three crystallographically independent enzyme subunits. The position of 7DHX overlapped with the positions occupied by purine bases in similar PNP complexes. However, the orientation of the 7DHX molecule differs from those of other bases: it is rotated by approximately 180 degrees relative to other bases. The peculiarities of the arrangement of 7DHX in the EcPNP active site are discussed. | |||
Crystal structure of Escherichia coli purine nucleoside phosphorylase in complex with 7-deazahypoxanthine.,Timofeev VI, Zhukhlistova NE, Abramchik YA, Fateev II, Kostromina MA, Muravieva TI, Esipov RS, Kuranova IP Acta Crystallogr F Struct Biol Commun. 2018 Jun 1;74(Pt 6):355-362. doi:, 10.1107/S2053230X18006337. Epub 2018 May 23. PMID:29870020<ref>PMID:29870020</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Abramchik | <div class="pdbe-citations 5iu6" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Timofeev | *[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Abramchik YA]] | |||
[[Category: Esipov RS]] | |||
[[Category: Kuranova IP]] | |||
[[Category: Timofeev VI]] | |||
Latest revision as of 17:09, 30 August 2023
Crystal structure of E.coli purine nucleoside phosphorylase with 7-deazahypoxanthineCrystal structure of E.coli purine nucleoside phosphorylase with 7-deazahypoxanthine
Structural highlights
FunctionDEOD_ECOLI Cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules.[HAMAP-Rule:MF_01627] Publication Abstract from PubMedPurine nucleoside phosphorylases (EC 2.4.2.1; PNPs) reversibly catalyze the phosphorolytic cleavage of glycosidic bonds in purine nucleosides to generate ribose 1-phosphate and a free purine base, and are key enzymes in the salvage pathway of purine biosynthesis. They also catalyze the transfer of pentosyl groups between purine bases (the transglycosylation reaction) and are widely used for the synthesis of biologically important analogues of natural nucleosides, including a number of anticancer and antiviral drugs. Potent inhibitors of PNPs are used in chemotherapeutic applications. The detailed study of the binding of purine bases and their derivatives in the active site of PNPs is of particular interest in order to understand the mechanism of enzyme action and for the development of new enzyme inhibitors. Here, it is shown that 7-deazahypoxanthine (7DHX) is a noncompetitive inhibitor of the phosphorolysis of inosine by recombinant Escherichia coli PNP (EcPNP) with an inhibition constant Ki of 0.13 mM. A crystal of EcPNP in complex with 7DHX was obtained in microgravity by the counter-diffusion technique and the three-dimensional structure of the EcPNP-7DHX complex was solved by molecular replacement at 2.51 A resolution using an X-ray data set collected at the SPring-8 synchrotron-radiation facility, Japan. The crystals belonged to space group P6122, with unit-cell parameters a = b = 120.370, c = 238.971 A, and contained three subunits of the hexameric enzyme molecule in the asymmetric unit. The 7DHX molecule was located with full occupancy in the active site of each of the three crystallographically independent enzyme subunits. The position of 7DHX overlapped with the positions occupied by purine bases in similar PNP complexes. However, the orientation of the 7DHX molecule differs from those of other bases: it is rotated by approximately 180 degrees relative to other bases. The peculiarities of the arrangement of 7DHX in the EcPNP active site are discussed. Crystal structure of Escherichia coli purine nucleoside phosphorylase in complex with 7-deazahypoxanthine.,Timofeev VI, Zhukhlistova NE, Abramchik YA, Fateev II, Kostromina MA, Muravieva TI, Esipov RS, Kuranova IP Acta Crystallogr F Struct Biol Commun. 2018 Jun 1;74(Pt 6):355-362. doi:, 10.1107/S2053230X18006337. Epub 2018 May 23. PMID:29870020[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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