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| - | {{STRUCTURE_4f95| PDB=4f95 | SCENE= }} | |
| - | ===Crystal structure of human inosine triphosphate pyrophosphatase P32T variant=== | |
| - | {{ABSTRACT_PUBMED_23528839}} | |
| | | | |
| - | ==Disease== | + | ==Crystal structure of human inosine triphosphate pyrophosphatase P32T variant== |
| - | [[http://www.uniprot.org/uniprot/ITPA_HUMAN ITPA_HUMAN]] Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:[http://omim.org/entry/613850 613850]]. It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Note=Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme.[:]<ref>PMID:12384777</ref> <ref>PMID:12436200</ref> | + | <StructureSection load='4f95' size='340' side='right'caption='[[4f95]], [[Resolution|resolution]] 2.07Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==Function== | + | <table><tr><td colspan='2'>[[4f95]] is a 1 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=4F95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F95 FirstGlance]. <br> |
| - | [[http://www.uniprot.org/uniprot/ITPA_HUMAN ITPA_HUMAN]] Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.<ref>PMID:17090528</ref> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.07Å</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=4f95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f95 OCA], [https://pdbe.org/4f95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f95 RCSB], [https://www.ebi.ac.uk/pdbsum/4f95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f95 ProSAT]</span></td></tr> |
| - | ==About this Structure== | + | </table> |
| - | [[4f95]] is a 1 chain structure with sequence 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=4F95 OCA].
| + | == Disease == |
| - | | + | [https://www.uniprot.org/uniprot/ITPA_HUMAN ITPA_HUMAN] Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:[https://omim.org/entry/613850 613850]. It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Note=Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme.[:]<ref>PMID:12384777</ref> <ref>PMID:12436200</ref> |
| - | ==Reference==
| + | == Function == |
| - | <references group="xtra"/><references/> | + | [https://www.uniprot.org/uniprot/ITPA_HUMAN ITPA_HUMAN] Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.<ref>PMID:17090528</ref> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Nucleoside-triphosphate diphosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Borgstahl, G E.O.]] | + | [[Category: Borgstahl GEO]] |
| - | [[Category: Pavlov, Y I.]] | + | [[Category: Pavlov YI]] |
| - | [[Category: Simone, P D.]] | + | [[Category: Simone PD]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Disease
ITPA_HUMAN Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850. It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Note=Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme.[:][1] [2]
Function
ITPA_HUMAN Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.[3]
References
- ↑ Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees DC, Thein SL, Ansari A, Sanderson J, De Abreu RA, Simmonds HA, Duley JA. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum Genet. 2002 Oct;111(4-5):360-7. Epub 2002 Aug 15. PMID:12384777 doi:10.1007/s00439-002-0798-z
- ↑ Cao H, Hegele RA. DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. J Hum Genet. 2002;47(11):620-2. PMID:12436200 doi:10.1007/s100380200095
- ↑ Burgis NE, Cunningham RP. Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase. J Biol Chem. 2007 Feb 9;282(6):3531-8. Epub 2006 Nov 6. PMID:17090528 doi:M608708200
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