2jk2: Difference between revisions
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< | ==STRUCTURAL BASIS OF HUMAN TRIOSEPHOSPHATE ISOMERASE DEFICIENCY. CRYSTAL STRUCTURE OF THE WILD TYPE ENZYME.== | ||
<StructureSection load='2jk2' size='340' side='right'caption='[[2jk2]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
You may change the | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jk2]] is a 2 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=2JK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JK2 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]] 1.7Å</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=2jk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jk2 OCA], [https://pdbe.org/2jk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jk2 RCSB], [https://www.ebi.ac.uk/pdbsum/2jk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jk2 ProSAT]</span></td></tr> | ||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:[https://omim.org/entry/190450 190450]. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_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/jk/2jk2_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=2jk2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human triosephosphate isomerase deficiency is a rare autosomal disease that causes premature death of homozygous individuals. The most frequent mutation that leads to this illness is in position 104, which involves a conservative change of a Glu for Asp. Despite the extensive work that has been carried out on the E104D mutant enzyme in hemolysates and whole cells, the molecular basis of this disease is poorly understood. Here, we show that the purified, recombinant mutant enzyme E104D, while exhibiting normal catalytic activity, shows impairments in the formation of active dimers and low thermostability and monomerizes under conditions in which the wild type retains its dimeric form. The crystal structure of the E104D mutant at 1.85 A resolution showed that its global structure was similar to that of the wild type; however, residue 104 is part of a conserved cluster of 10 residues, five from each subunit. An analysis of the available high resolution structures of TIM dimers revealed that this cluster forms a cavity that possesses an elaborate conserved network of buried water molecules that bridge the two subunits. In the E104D mutant, a disruption of contacts of the amino acid side chains in the conserved cluster leads to a perturbation of the water network in which the water-protein and water-water interactions that join the two monomers are significantly weakened and diminished. Thus, the disruption of this solvent system would stand as the underlying cause of the deficiency. | |||
Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface.,Rodriguez-Almazan C, Arreola R, Rodriguez-Larrea D, Aguirre-Lopez B, de Gomez-Puyou MT, Perez-Montfort R, Costas M, Gomez-Puyou A, Torres-Larios A J Biol Chem. 2008 Aug 22;283(34):23254-63. Epub 2008 Jun 18. PMID:18562316<ref>PMID:18562316</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jk2" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Triose phosphate isomerase 3D structures|Triose phosphate isomerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Aguirre-Lopez | [[Category: Aguirre-Lopez B]] | ||
[[Category: Arreola-Alemon | [[Category: Arreola-Alemon R]] | ||
[[Category: Costas | [[Category: Costas M]] | ||
[[Category: Gomez-Puyou | [[Category: De Gomez-Puyou MT]] | ||
[[Category: Gomez-Puyou | [[Category: Gomez-Puyou A]] | ||
[[Category: Perez-Montfort | [[Category: Perez-Montfort R]] | ||
[[Category: Rodriguez-Almazan | [[Category: Rodriguez-Almazan C]] | ||
[[Category: Rodriguez-Larrea | [[Category: Rodriguez-Larrea D]] | ||
[[Category: Torres-Larios | [[Category: Torres-Larios A]] | ||
Latest revision as of 17:52, 13 December 2023
STRUCTURAL BASIS OF HUMAN TRIOSEPHOSPHATE ISOMERASE DEFICIENCY. CRYSTAL STRUCTURE OF THE WILD TYPE ENZYME.STRUCTURAL BASIS OF HUMAN TRIOSEPHOSPHATE ISOMERASE DEFICIENCY. CRYSTAL STRUCTURE OF THE WILD TYPE ENZYME.
Structural highlights
DiseaseTPIS_HUMAN Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:190450. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman triosephosphate isomerase deficiency is a rare autosomal disease that causes premature death of homozygous individuals. The most frequent mutation that leads to this illness is in position 104, which involves a conservative change of a Glu for Asp. Despite the extensive work that has been carried out on the E104D mutant enzyme in hemolysates and whole cells, the molecular basis of this disease is poorly understood. Here, we show that the purified, recombinant mutant enzyme E104D, while exhibiting normal catalytic activity, shows impairments in the formation of active dimers and low thermostability and monomerizes under conditions in which the wild type retains its dimeric form. The crystal structure of the E104D mutant at 1.85 A resolution showed that its global structure was similar to that of the wild type; however, residue 104 is part of a conserved cluster of 10 residues, five from each subunit. An analysis of the available high resolution structures of TIM dimers revealed that this cluster forms a cavity that possesses an elaborate conserved network of buried water molecules that bridge the two subunits. In the E104D mutant, a disruption of contacts of the amino acid side chains in the conserved cluster leads to a perturbation of the water network in which the water-protein and water-water interactions that join the two monomers are significantly weakened and diminished. Thus, the disruption of this solvent system would stand as the underlying cause of the deficiency. Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface.,Rodriguez-Almazan C, Arreola R, Rodriguez-Larrea D, Aguirre-Lopez B, de Gomez-Puyou MT, Perez-Montfort R, Costas M, Gomez-Puyou A, Torres-Larios A J Biol Chem. 2008 Aug 22;283(34):23254-63. Epub 2008 Jun 18. PMID:18562316[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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