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| - | {{Seed}} | |
| - | [[Image:1qo5.png|left|200px]] | |
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| - | <!-- | + | ==Fructose 1,6-bisphosphate Aldolase from Human Liver Tissue== |
| - | The line below this paragraph, containing "STRUCTURE_1qo5", creates the "Structure Box" on the page.
| + | <StructureSection load='1qo5' size='340' side='right'caption='[[1qo5]], [[Resolution|resolution]] 2.50Å' 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'>[[1qo5]] is a 18 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=1QO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QO5 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]] 2.5Å</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> |
| - | {{STRUCTURE_1qo5| PDB=1qo5 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qo5 OCA], [https://pdbe.org/1qo5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qo5 RCSB], [https://www.ebi.ac.uk/pdbsum/1qo5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qo5 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/qo/1qo5_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=1qo5 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The X-ray crystallographic structure of the human liver isozyme of fructose-1,6-bisphosphate aldolase has been determined by molecular replacement using a tetramer of the human muscle isozyme as a search model. The liver aldolase (B isozyme) crystallized in space group C2, with unit-cell parameters a = 291.1, b = 489.8, c = 103.4 A, alpha = 90, beta = 103.6, gamma = 90 degrees. These large unit-cell parameters result from the presence of 18 subunits in the asymmetric unit: four catalytic tetramers and a dimer from a fifth tetramer positioned on the twofold crystallographic axis. This structure provides further insight into the factors affecting isozyme specificity. It reveals small differences in secondary structure that occur in regions previously determined to be isozyme specific. Two of these regions are at the solvent-exposed enzyme surface away from the active site of the enzyme. The most significant changes are in the flexible C-terminal region of the enzyme, where there is an insertion of an extra alpha-helix. Point mutations of the human liver aldolase are responsible for the disease hereditary fructose intolerance. Sequence information is projected onto the new crystal structure in order to indicate how these mutations bring about reduced enzyme activity and affect structural stability. |
| | | | |
| - | ===FRUCTOSE 1,6-BISPHOSPHATE ALDOLASE FROM HUMAN LIVER TISSUE===
| + | The structure of human liver fructose-1,6-bisphosphate aldolase.,Dalby AR, Tolan DR, Littlechild JA Acta Crystallogr D Biol Crystallogr. 2001 Nov;57(Pt 11):1526-33. Epub 2001, Oct 25. PMID:11679716<ref>PMID:11679716</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1qo5" style="background-color:#fffaf0;"></div> |
| | | | |
| - | <!--
| + | ==See Also== |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_11679716}}, adds the Publication Abstract to the page
| + | *[[Aldolase 3D structures|Aldolase 3D structures]] |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 11679716 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_11679716}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | |
| - | 1QO5 is a 18 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=1QO5 OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:11679716</ref><references group="xtra"/> | + | |
| - | [[Category: Fructose-bisphosphate aldolase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Dalby, A R.]] | + | [[Category: Large Structures]] |
| - | [[Category: Littlechild, J A.]] | + | [[Category: Dalby AR]] |
| - | [[Category: Aldolase]] | + | [[Category: Littlechild JA]] |
| - | [[Category: Glycolytic enzyme]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Sep 3 16:22:25 2009''
| + | |
| Structural highlights
Disease
ALDOB_HUMAN Defects in ALDOB are the cause of hereditary fructose intolerance (HFI) [MIM: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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
Function
ALDOB_HUMAN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The X-ray crystallographic structure of the human liver isozyme of fructose-1,6-bisphosphate aldolase has been determined by molecular replacement using a tetramer of the human muscle isozyme as a search model. The liver aldolase (B isozyme) crystallized in space group C2, with unit-cell parameters a = 291.1, b = 489.8, c = 103.4 A, alpha = 90, beta = 103.6, gamma = 90 degrees. These large unit-cell parameters result from the presence of 18 subunits in the asymmetric unit: four catalytic tetramers and a dimer from a fifth tetramer positioned on the twofold crystallographic axis. This structure provides further insight into the factors affecting isozyme specificity. It reveals small differences in secondary structure that occur in regions previously determined to be isozyme specific. Two of these regions are at the solvent-exposed enzyme surface away from the active site of the enzyme. The most significant changes are in the flexible C-terminal region of the enzyme, where there is an insertion of an extra alpha-helix. Point mutations of the human liver aldolase are responsible for the disease hereditary fructose intolerance. Sequence information is projected onto the new crystal structure in order to indicate how these mutations bring about reduced enzyme activity and affect structural stability.
The structure of human liver fructose-1,6-bisphosphate aldolase.,Dalby AR, Tolan DR, Littlechild JA Acta Crystallogr D Biol Crystallogr. 2001 Nov;57(Pt 11):1526-33. Epub 2001, Oct 25. PMID:11679716[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Santamaria R, Esposito G, Vitagliano L, Race V, Paglionico I, Zancan L, Zagari A, Salvatore F. Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase. Biochem J. 2000 Sep 15;350 Pt 3:823-8. PMID:10970798
- ↑ Cross NC, Tolan DR, Cox TM. Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation. Cell. 1988 Jun 17;53(6):881-5. PMID:3383242
- ↑ Cross NC, de Franchis R, Sebastio G, Dazzo C, Tolan DR, Gregori C, Odievre M, Vidailhet M, Romano V, Mascali G, et al.. Molecular analysis of aldolase B genes in hereditary fructose intolerance. Lancet. 1990 Feb 10;335(8685):306-9. PMID:1967768
- ↑ Brooks CC, Tolan DR. A partially active mutant aldolase B from a patient with hereditary fructose intolerance. FASEB J. 1994 Jan;8(1):107-13. PMID:8299883
- ↑ Ali M, Sebastio G, Cox TM. Identification of a novel mutation (Leu 256-->Pro) in the human aldolase B gene associated with hereditary fructose intolerance. Hum Mol Genet. 1994 Jan;3(1):203-4. PMID:8162030
- ↑ Cross NC, Stojanov LM, Cox TM. A new aldolase B variant, N334K, is a common cause of hereditary fructose intolerance in Yugoslavia. Nucleic Acids Res. 1990 Apr 11;18(7):1925. PMID:2336380
- ↑ Lau J, Tolan DR. Screening for hereditary fructose intolerance mutations by reverse dot-blot. Mol Cell Probes. 1999 Feb;13(1):35-40. PMID:10024431 doi:S0890-8508(98)90208-0
- ↑ Sanchez-Gutierrez JC, Benlloch T, Leal MA, Samper B, Garcia-Ripoll I, Feliu JE. Molecular analysis of the aldolase B gene in patients with hereditary fructose intolerance from Spain. J Med Genet. 2002 Sep;39(9):e56. PMID:12205126
- ↑ Esposito G, Santamaria R, Vitagliano L, Ieno L, Viola A, Fiori L, Parenti G, Zancan L, Zagari A, Salvatore F. Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene. Hum Mutat. 2004 Dec;24(6):534. PMID:15532022 doi:10.1002/humu.9290
- ↑ Santer R, Rischewski J, von Weihe M, Niederhaus M, Schneppenheim S, Baerlocher K, Kohlschutter A, Muntau A, Posselt HG, Steinmann B, Schneppenheim R. The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Hum Mutat. 2005 Jun;25(6):594. PMID:15880727 doi:10.1002/humu.9343
- ↑ Dalby AR, Tolan DR, Littlechild JA. The structure of human liver fructose-1,6-bisphosphate aldolase. Acta Crystallogr D Biol Crystallogr. 2001 Nov;57(Pt 11):1526-33. Epub 2001, Oct 25. PMID:11679716
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