View source for 1xdl


==Structure of human aldolase B associated with hereditary fructose intolerance (A149P), at 277K==
<StructureSection load='1xdl' size='340' side='right'caption='[[1xdl]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xdl]] is a 8 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=1XDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XDL 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1xdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xdl OCA], [https://pdbe.org/1xdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xdl RCSB], [https://www.ebi.ac.uk/pdbsum/1xdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xdl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ALDOB_HUMAN ALDOB_HUMAN] Defects in ALDOB are the cause of hereditary fructose intolerance (HFI) [MIM:[https://omim.org/entry/229600 229600]. HFI is an autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.<ref>PMID:10970798</ref> <ref>PMID:3383242</ref> <ref>PMID:1967768</ref> <ref>PMID:8299883</ref> <ref>PMID:8162030</ref> <ref>PMID:2336380</ref> <ref>PMID:10024431</ref> <ref>PMID:12205126</ref> <ref>PMID:15532022</ref> <ref>PMID:15880727</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ALDOB_HUMAN ALDOB_HUMAN] 
== 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/xd/1xdl_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=1xdl ConSurf].
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== Publication Abstract from PubMed ==
Hereditary fructose intolerance (HFI) is a potentially lethal inborn error in metabolism caused by mutations in the aldolase B gene, which is critical for gluconeogenesis and fructose metabolism. The most common mutation, which accounts for 53% of HFI alleles identified worldwide, results in substitution of Pro for Ala at position 149. Structural and functional investigations of human aldolase B with the A149P substitution (AP-aldolase) have shown that the mutation leads to losses in thermal stability, quaternary structure, and activity. X-ray crystallography is used to reveal the structural basis of these perturbations. Crystals of AP-aldolase are grown at two temperatures (4 degrees C and 18 degrees C), and the structure solved to 3.0 angstroms resolution, using the wild-type structure as the phasing model. The structures reveal that the single residue substitution, A149P, causes molecular disorder around the site of mutation (residues 148-159), which is propagated to three adjacent beta-strand and loop regions (residues 110-129, 189-199, 235-242). Disorder in the 110-129-loop region, which comprises one subunit-subunit interface, provides an explanation for the disrupted quaternary structure and thermal instability. Greater structural perturbation, particularly at a Glu189-Arg148 salt bridge in the active-site architecture, is observed in the structure determined at 18 degrees C, which could explain the temperature-dependent loss in activity. The disorder revealed in these structures is far greater than that predicted by homology modeling and underscores the difficulties in predicting perturbations of protein structure and function by homology modeling alone. The AP-aldolase structure reveals the molecular basis of a hereditary disease and represents one of only a few structures known for mutant proteins at the root of the thousands of other inherited disorders.

Structure of the thermolabile mutant aldolase B, A149P: molecular basis of hereditary fructose intolerance.,Malay AD, Allen KN, Tolan DR J Mol Biol. 2005 Mar 18;347(1):135-44. Epub 2005 Jan 20. PMID:15733923<ref>PMID:15733923</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 1xdl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldolase 3D structures|Aldolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allen KN]]
[[Category: Malay AD]]
[[Category: Tolan DR]]