View source for 1fta


==FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE, 1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH THE ALLOSTERIC INHIBITOR AMP==
<StructureSection load='1fta' size='340' side='right'caption='[[1fta]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fta]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FTA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1FTA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1fta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fta OCA], [http://pdbe.org/1fta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fta RCSB], [http://www.ebi.ac.uk/pdbsum/1fta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fta ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN]] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:[http://omim.org/entry/229700 229700]]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.<ref>PMID:9382095</ref> <ref>PMID:12126934</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/ft/1fta_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=1fta ConSurf].
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== Publication Abstract from PubMed ==
The molecular structure of human liver fructose-1,6-bisphosphatase complexed with AMP was determined by x-ray diffraction using molecular replacement, starting from the pig kidney enzyme AMP complex. Of the 34 amino acid residues which differ between these two sequences, only one interacts with AMP; Met30 in pig kidney is Leu30 in human liver. From this analysis, six sites in which side chains of amino acid residues are in contact with AMP, Ala24, Leu30, Thr31, Tyr113, Arg140, and Met177, were mutated by polymerase chain reaction. The wild-type and mutant forms were expressed in Escherichia coli, purified, and their kinetic properties determined. Circular dichroism spectra of the mutants were indistinguishable from that of the wild-type enzyme. Kinetic analyses revealed that all forms had similar turnover numbers, Km values for fructose 2,6-bisphosphate, and inhibition constants for fructose 2,6-bisphosphate. Apparent Ki values for AMP inhibition of the Leu30 --&gt; Phe and Met177 --&gt; Ala mutants were similar to those of the wild-type enzyme, but the apparent Ki values for the Arg140 --&gt; Ala and Ala24 --&gt; Phe mutants were 7-to 20-fold higher, respectively. The Thr31 --&gt; Ser mutant exhibited a 5-fold increase in apparent Ki for AMP, while mutation of Thr31 to Ala increased the apparent Ki 120-fold. AMP inhibition of the Tyr113 --&gt; Phe mutant was undetectable even at millimolar AMP concentrations. Fructose 2,6-bisphosphate potentiated AMP inhibition of the mutants to the same extent as for the wild-type enzyme, except in the case of the Thr31 --&gt; Ala and Tyr113 --&gt; Phe mutants. Thus, the Met177 --&gt; Ala mutant suggests that the side chain beyond C alpha is not needed for AMP binding, and that the Leu30 --&gt; Phe mutant preserves the AMP contacts with these side chains. Thr31, Tyr113, and Arg140 form key hydrogen bonds to AMP consistent with strong side chain interactions in the wild-type enzyme. Finally, the absence of any effect of fructose 2,6-bisphosphate on AMP inhibition observed in the Thr31 --&gt; Ala mutant may be an important clue relating to the mechanism of synergism of these two inhibitors.

The allosteric site of human liver fructose-1,6-bisphosphatase. Analysis of six AMP site mutants based on the crystal structure.,Gidh-Jain M, Zhang Y, van Poelje PD, Liang JY, Huang S, Kim J, Elliott JT, Erion MD, Pilkis SJ, Raafat el-Maghrabi M, et al. J Biol Chem. 1994 Nov 4;269(44):27732-8. PMID:7961695<ref>PMID:7961695</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1fta" style="background-color:#fffaf0;"></div>

==See Also==
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Fructose-bisphosphatase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Huang, S]]
[[Category: Liang, J Y]]
[[Category: Lipscomb, W N]]
[[Category: Zhang, Y]]