2i5d

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Revision as of 08:23, 18 October 2017

Crystal Structure of Human Inosine Triphosphate Pyrophosphatase

Structural highlights

2i5d is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2car
Gene:	ITPA, C20orf37 (HUMAN)
Activity:	Nucleoside-triphosphate diphosphatase, with EC number 3.6.1.19
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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 structure of human inosine triphosphate pyrophosphohydrolase (ITPA) has been determined using diffraction data to 1.6 A resolution. ITPA contributes to the accurate replication of DNA by cleansing cellular dNTP pools of mutagenic nucleotide purine analogs such as dITP or dXTP. A similar high-resolution unpublished structure has been deposited in the Protein Data Bank from a monoclinic and pseudo-merohedrally twinned crystal. Here, cocrystallization of ITPA with a molar ratio of XTP appears to have improved the crystals by eliminating twinning and resulted in an orthorhombic space group. However, there was no evidence for bound XTP in the structure. Comparison with substrate-bound NTPase from a thermophilic organism predicts the movement of residues within helix alpha1, the loop before alpha6 and helix alpha7 to cap off the active site when substrate is bound.

Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase.,Porta J, Kolar C, Kozmin SG, Pavlov YI, Borgstahl GE Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Nov 1;62(Pt, 11):1076-81. Epub 2006 Oct 25. PMID:17077483^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Porta J, Kolar C, Kozmin SG, Pavlov YI, Borgstahl GE. Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Nov 1;62(Pt, 11):1076-81. Epub 2006 Oct 25. PMID:17077483 doi:10.1107/S1744309106041790

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2i5d"

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 ==Crystal Structure of Human Inosine Triphosphate Pyrophosphatase==
 <StructureSection load='2i5d' size='340' side='right' caption='[[2i5d]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITPA, C20orf37 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i5d OCA], [http://pdbe.org/2i5d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i5d RCSB], [http://www.ebi.ac.uk/pdbsum/2i5d PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i5d OCA], [http://pdbe.org/2i5d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i5d RCSB], [http://www.ebi.ac.uk/pdbsum/2i5d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i5d ProSAT]</span></td></tr>
 </table>
 == Disease ==

2i5d

From Proteopedia

Revision as of 08:23, 18 October 2017

Crystal Structure of Human Inosine Triphosphate Pyrophosphatase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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