|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Thymidine phosphorylase from E.coli with 3'-azido-3'-deoxythymidine== | | ==Thymidine phosphorylase from E.coli with 3'-azido-3'-deoxythymidine== |
| - | <StructureSection load='4lhm' size='340' side='right' caption='[[4lhm]], [[Resolution|resolution]] 1.52Å' scene=''> | + | <StructureSection load='4lhm' size='340' side='right'caption='[[4lhm]], [[Resolution|resolution]] 1.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lhm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LHM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LHM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lhm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LHM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZZ:3-AZIDO-3-DEOXYTHYMIDINE'>AZZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZZ:3-AZIDO-3-DEOXYTHYMIDINE'>AZZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">deoA, tpp, ttg, b4382, JW4345 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=4lhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhm OCA], [https://pdbe.org/4lhm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lhm RCSB], [https://www.ebi.ac.uk/pdbsum/4lhm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhm ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidine_phosphorylase Thymidine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.4 2.4.2.4] </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=4lhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhm OCA], [http://pdbe.org/4lhm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lhm RCSB], [http://www.ebi.ac.uk/pdbsum/4lhm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYPH_ECOLI TYPH_ECOLI]] The enzymes which catalyze the reversible phosphorolysis of pyrimidine nucleosides are involved in the degradation of these compounds and in their utilization as carbon and energy sources, or in the rescue of pyrimidine bases for nucleotide synthesis. | + | [https://www.uniprot.org/uniprot/TYPH_ECOLI TYPH_ECOLI] The enzymes which catalyze the reversible phosphorolysis of pyrimidine nucleosides are involved in the degradation of these compounds and in their utilization as carbon and energy sources, or in the rescue of pyrimidine bases for nucleotide synthesis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Thymidine phosphorylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Abramchik, Y A]] | + | [[Category: Abramchik YA]] |
| - | [[Category: Esipov, R S]] | + | [[Category: Esipov RS]] |
| - | [[Category: Kuranova, I P]] | + | [[Category: Kuranova IP]] |
| - | [[Category: Timofeev, V I]] | + | [[Category: Timofeev VI]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TYPH_ECOLI The enzymes which catalyze the reversible phosphorolysis of pyrimidine nucleosides are involved in the degradation of these compounds and in their utilization as carbon and energy sources, or in the rescue of pyrimidine bases for nucleotide synthesis.
Publication Abstract from PubMed
The structural study of complexes of thymidine phosphorylase (TP) with nucleoside analogues which inhibit its activity is of special interest because many of these compounds are used as chemotherapeutic agents. Determination of kinetic parameters showed that 3'-azido-3'-deoxythymidine (3'-azidothymidine; AZT), which is widely used for the treatment of human immunodeficiency virus, is a reversible noncompetitive inhibitor of Escherichia coli thymidine phosphorylase (TP). The three-dimensional structure of E. coli TP complexed with AZT was solved by the molecular-replacement method and was refined at 1.52 A resolution. Crystals for X-ray study were grown in microgravity by the counter-diffusion technique from a solution of the protein in phosphate buffer with ammonium sulfate as a precipitant. The AZT molecule was located with full occupancy in the electron-density maps in the nucleoside-binding pocket of TP, whereas the phosphate-binding pocket of the enzyme was occupied by phosphate (or sulfate) ion. The structure of the active-site cavity and conformational changes of the enzyme upon AZT binding are described in detail. It is found that the position of AZT differs remarkably from the positions of the pyrimidine bases and nucleoside analogues in other known complexes of pyrimidine phosphorylases, but coincides well with the position of 2'-fluoro-3'-azido-2',3'-dideoxyuridine (N3FddU) in the recently investigated complex of E. coli TP with this ligand (Timofeev et al., 2013). The peculiarities of the arrangement of N3FddU and 3'-azidothymidine in the nucleoside binding pocket of TP and correlations between the arrangement and inhibitory properties of these compounds are discussed.
3'-Azidothymidine in the active site of Escherichia coli thymidine phosphorylase: the peculiarity of the binding on the basis of X-ray study.,Timofeev V, Abramchik Y, Zhukhlistova N, Muravieva T, Fateev I, Esipov R, Kuranova I Acta Crystallogr D Biol Crystallogr. 2014 Apr;70(Pt 4):1155-65. doi:, 10.1107/S1399004714001904. Epub 2014 Mar 21. PMID:24699659[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Timofeev V, Abramchik Y, Zhukhlistova N, Muravieva T, Fateev I, Esipov R, Kuranova I. 3'-Azidothymidine in the active site of Escherichia coli thymidine phosphorylase: the peculiarity of the binding on the basis of X-ray study. Acta Crystallogr D Biol Crystallogr. 2014 Apr;70(Pt 4):1155-65. doi:, 10.1107/S1399004714001904. Epub 2014 Mar 21. PMID:24699659 doi:http://dx.doi.org/10.1107/S1399004714001904
|
