2j4e: Difference between revisions
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==THE ITP COMPLEX OF HUMAN INOSINE TRIPHOSPHATASE== | ==THE ITP COMPLEX OF HUMAN INOSINE TRIPHOSPHATASE== | ||
<StructureSection load='2j4e' size='340' side='right' caption='[[2j4e]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='2j4e' size='340' side='right'caption='[[2j4e]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2j4e]] is a 8 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=2J4E OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2j4e]] is a 8 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=2J4E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2J4E FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=ITT:INOSINE+5-TRIPHOSPHATE'>ITT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=ITT:INOSINE+5-TRIPHOSPHATE'>ITT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2car|2car]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2car|2car]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nucleoside-triphosphate_diphosphatase Nucleoside-triphosphate diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.19 3.6.1.19] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nucleoside-triphosphate_diphosphatase Nucleoside-triphosphate diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.19 3.6.1.19] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2j4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j4e OCA], [http://pdbe.org/2j4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j4e RCSB], [http://www.ebi.ac.uk/pdbsum/2j4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j4e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Nucleoside-triphosphate diphosphatase]] | [[Category: Nucleoside-triphosphate diphosphatase]] | ||
[[Category: Arrowsmith, C]] | [[Category: Arrowsmith, C]] | ||
Revision as of 10:39, 15 April 2020
THE ITP COMPLEX OF HUMAN INOSINE TRIPHOSPHATASETHE ITP COMPLEX OF HUMAN INOSINE TRIPHOSPHATASE
Structural highlights
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 PubMedInosine triphosphatase (ITPA) is a ubiquitous key regulator of cellular non-canonical nucleotide levels. It breaks down inosine and xanthine nucleotides generated by deamination of purine bases. Its enzymatic action prevents accumulation of ITP and reduces the risk of incorporation of potentially mutagenic inosine nucleotides into nucleic acids. Here we describe the crystal structure of human ITPA in complex with its prime substrate ITP, as well as the apoenzyme at 2.8 and 1.1A, respectively. These structures show for the first time the site of substrate and Mg2+ coordination as well as the conformational changes accompanying substrate binding in this class of enzymes. Enzyme substrate interactions induce an extensive closure of the nucleotide binding grove, resulting in tight interactions with the base that explain the high substrate specificity of ITPA for inosine and xanthine over the canonical nucleotides. One of the dimer contact sites is made up by a loop that is involved in coordinating the metal ion in the active site. We predict that the ITPA deficiency mutation P32T leads to a shift of this loop that results in a disturbed affinity for nucleotides and/or a reduced catalytic activity in both monomers of the physiological dimer. Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T.,Stenmark P, Kursula P, Flodin S, Graslund S, Landry R, Nordlund P, Schuler H J Biol Chem. 2007 Feb 2;282(5):3182-7. Epub 2006 Nov 29. PMID:17138556[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Human
- Large Structures
- Nucleoside-triphosphate diphosphatase
- Arrowsmith, C
- Berg, S Van Den
- Berglund, H
- Busam, R
- Collins, R
- Edwards, A
- Ehn, M
- Flodin, S
- Flores, A
- Graslund, S
- Hallberg, B M
- Hammarstrom, M
- Hogbom, M
- Holmbergschiavone, L
- Kotenyova, T
- Kursula, P
- Landry, R
- Loppnau, P
- Magnusdottir, A
- Nilsson-Ehle, P
- Nordlund, P
- Nyman, T
- Ogg, D
- Persson, C
- Sagemark, J
- Schuler, H
- Stenmark, P
- Sundstrom, M
- Thorsell, A G
- Uppenberg, J
- Wallden, K
- Weigelt, J
- Disease mutation
- Hydrolase
- Imp
- Inosine triphosphatase deficiency
- Inosine triphosphate pyrophosphohydrolase
- Itp
- Nucleotide metabolism