View source for 5tle


==Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with the inhibitor 2-phosphate-naphthalene 6-bisphosphonate==
<StructureSection load='5tle' size='340' side='right'caption='[[5tle]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tle]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TLE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RD1:{[6-(phosphonooxy)naphthalen-2-yl]methylene}bis(phosphonic+acid)'>RD1</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=5tle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tle OCA], [https://pdbe.org/5tle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tle RCSB], [https://www.ebi.ac.uk/pdbsum/5tle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tle ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ALDOA_RABIT ALDOA_RABIT] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.<ref>PMID:17329259</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The glycolytic enzyme aldolase is an emerging drug target in diseases such as cancer and protozoan infections which are dependent on a hyperglycolytic phenotype to synthesize adenosine 5'-triphosphate and metabolic precursors for biomass production. To date, structural information for the enzyme in complex with phosphate-derived inhibitors has been lacking. Thus, we determined the crystal structure of mammalian aldolase in complex with naphthalene 2,6-bisphosphate (1) that served as a template for the design of bisphosphonate-based inhibitors, namely, 2-phosphate-naphthalene 6-bisphosphonate (2), 2-naphthol 6-bisphosphonate (3), and 1-phosphate-benzene 4-bisphosphonate (4). All inhibitors targeted the active site, and the most promising lead, 2, exhibited slow-binding inhibition with an overall inhibition constant of approximately 38 nM. Compound 2 inhibited proliferation of HeLa cancer cells, whereas HEK293 cells expressing a normal phenotype were not inhibited. The crystal structures delineated the essential features of high-affinity phosphate-derived inhibitors and provide a template for the development of inhibitors with prophylaxis potential.

Bisphosphonate Inhibitors of Mammalian Glycolytic Aldolase.,Heron PW, Abellan-Flos M, Salmon L, Sygusch J J Med Chem. 2018 Dec 13;61(23):10558-10572. doi: 10.1021/acs.jmedchem.8b01000., Epub 2018 Dec 3. PMID:30418024<ref>PMID:30418024</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5tle" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldolase 3D structures|Aldolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Heron PW]]
[[Category: Sygusch J]]