View source for 5oez


==Crystal structure of Leishmania major fructose-1,6-bisphosphatase in apo form.==
<StructureSection load='5oez' size='340' side='right'caption='[[5oez]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5oez]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OEZ 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]] 2.41&#8491;</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=5oez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oez OCA], [https://pdbe.org/5oez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oez RCSB], [https://www.ebi.ac.uk/pdbsum/5oez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oez ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O97193_LEIMA O97193_LEIMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The gluconeogenic enzyme fructose-1,6-bisphosphatase has been proposed as a potential drug target against Leishmania parasites that cause up to 20,000-30,000 deaths annually. A comparison of three crystal structures of L. major fructose-1,6-bisphosphatase (LmFBPase) along with enzyme kinetic data show how AMP acts as an allosteric inhibitor and provides insight into its metal-dependent reaction mechanism. The crystal structure of the apoenzyme form of LmFBPase is a homotetramer in which the dimer of dimers adopts a planar conformation with disordered 'dynamic loops'. The structure of LmFBPase, complexed with manganese and its catalytic product phosphate shows the dynamic loops locked into the active sites. A third crystal structure of LmFBPase complexed with its allosteric inhibitor AMP shows an inactive form of the tetramer, in which the dimer pairs are rotated by 18 degrees relative to each other. The three structures suggest an allosteric mechanism in which AMP binding triggers a rearrangement of hydrogen-bonds across the large and small interfaces. Retraction of the 'effector loop' required for AMP binding releases the side chain of His23 from the dimer-dimer interface. This is coupled with a flip of the side chain of Arg48 which ties down the key catalytic dynamic loop in a disengaged conformation and also locks the tetramer in an inactive rotated T-state. The structure of the effector site of LmFBPase shows different structural features compared with human FBPases, thereby offering a potential and species-specific drug target.

Structures of Leishmania Fructose-1,6-bisphosphatase Reveal Species-Specific Differences in the Mechanism of Allosteric Inhibition.,Yuan M, Vasquez-Valdivieso MG, McNae I, Michels PAM, Fothergill-Gilmore LA, Walkinshaw MD J Mol Biol. 2017 Sep 4. pii: S0022-2836(17)30416-3. doi:, 10.1016/j.jmb.2017.08.010. PMID:28882541<ref>PMID:28882541</ref>

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

==See Also==
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania major]]
[[Category: Fothergill-Gilmore LA]]
[[Category: McNae IW]]
[[Category: Michels PAM]]
[[Category: Vasquez-Valdivieso MG]]
[[Category: Walkinshaw MD]]
[[Category: Yuan M]]