2j0f

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:31, 13 December 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:2j0f.png|left|200px]]
 
-
<!--
+
==Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implication for drug design==
-
The line below this paragraph, containing "STRUCTURE_2j0f", creates the "Structure Box" on the page.
+
<StructureSection load='2j0f' size='340' side='right'caption='[[2j0f]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[2j0f]] is a 4 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=2J0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J0F FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TDR:THYMINE'>TDR</scene></td></tr>
-
{{STRUCTURE_2j0f| PDB=2j0f | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0f OCA], [https://pdbe.org/2j0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j0f RCSB], [https://www.ebi.ac.uk/pdbsum/2j0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j0f ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/TYPH_HUMAN TYPH_HUMAN] Mitochondrial neurogastrointestinal encephalomyopathy. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9924029</ref> <ref>PMID:12177387</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TYPH_HUMAN TYPH_HUMAN] May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.<ref>PMID:1590793</ref> Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.<ref>PMID:1590793</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j0/2j0f_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j0f ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
HTP (human thymidine phosphorylase), also known as PD-ECGF (platelet-derived endothelial cell growth factor) or gliostatin, has an important role in nucleoside metabolism. HTP is implicated in angiogenesis and apoptosis and therefore is a prime target for drug design, including antitumour therapies. An HTP structure in a closed conformation complexed with an inhibitor has previously been solved. Earlier kinetic studies revealed an ordered release of thymine followed by ribose phosphate and product inhibition by both ligands. We have determined the structure of HTP from crystals grown in the presence of thymidine, which, surprisingly, resulted in bound thymine with HTP in a closed dead-end complex. Thus thymine appears to be able to reassociate with HTP after its initial ordered release before ribose phosphate and induces the closed conformation, hence explaining the mechanism of non-competitive product inhibition. In the active site in one of the four HTP molecules within the crystal asymmetric unit, additional electron density is present. This density has not been previously seen in any pyrimidine nucleoside phosphorylase and it defines a subsite that may be exploitable in drug design. Finally, because our crystals did not require proteolysed HTP to grow, the structure reveals a loop (residues 406-415), disordered in the previous HTP structure. This loop extends across the active-site cleft and appears to stabilize the dimer interface and the closed conformation by hydrogen-bonding. The present study will assist in the design of HTP inhibitors that could lead to drugs for anti-angiogenesis as well as for the potentiation of other nucleoside drugs.
-
===STRUCTURAL BASIS FOR NON-COMPETITIVE PRODUCT INHIBITION IN HUMAN THYMIDINE PHOSPHORYLASE: IMPLICATION FOR DRUG DESIGN===
+
Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design.,El Omari K, Bronckaers A, Liekens S, Perez-Perez MJ, Balzarini J, Stammers DK Biochem J. 2006 Oct 15;399(2):199-204. PMID:16803458<ref>PMID:16803458</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
==About this Structure==
+
</div>
-
2J0F is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0F OCA].
+
<div class="pdbe-citations 2j0f" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Thymidine phosphorylase]]
+
[[Category: Large Structures]]
-
[[Category: Balzarini, J.]]
+
[[Category: Balzarini J]]
-
[[Category: Bronckaers, A.]]
+
[[Category: Bronckaers A]]
-
[[Category: Liekens, S.]]
+
[[Category: El Omari K]]
-
[[Category: Omari, K El.]]
+
[[Category: Liekens S]]
-
[[Category: Perez-Perez, M J.]]
+
[[Category: Perez-Perez MJ]]
-
[[Category: Stammers, D K.]]
+
[[Category: Stammers DK]]
-
[[Category: Angiogenesis]]
+
-
[[Category: Chemotaxis]]
+
-
[[Category: Developmental protein]]
+
-
[[Category: Differentiation]]
+
-
[[Category: Disease mutation]]
+
-
[[Category: Glycosyltransferase]]
+
-
[[Category: Growth factor]]
+
-
[[Category: Htp]]
+
-
[[Category: Human thymidine phosphorylase]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Transferase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 20:21:33 2009''
+

Current revision

Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implication for drug design

PDB ID 2j0f

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2j0f"
Personal tools