2i5d

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "2i5d" [edit=sysop:move=sysop])
Line 1: Line 1:
-
[[Image:2i5d.png|left|200px]]
 
- 
{{STRUCTURE_2i5d| PDB=2i5d | SCENE= }}
{{STRUCTURE_2i5d| PDB=2i5d | SCENE= }}
- 
===Crystal Structure of Human Inosine Triphosphate Pyrophosphatase===
===Crystal Structure of Human Inosine Triphosphate Pyrophosphatase===
 +
{{ABSTRACT_PUBMED_17077483}}
-
{{ABSTRACT_PUBMED_17077483}}
+
==Disease==
 +
[[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>
 +
 
 +
==Function==
 +
[[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>
==About this Structure==
==About this Structure==
Line 11: Line 13:
==Reference==
==Reference==
-
<ref group="xtra">PMID:017077483</ref><references group="xtra"/>
+
<ref group="xtra">PMID:017077483</ref><references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Nucleoside-triphosphate diphosphatase]]
[[Category: Nucleoside-triphosphate diphosphatase]]

Revision as of 02:03, 25 March 2013

Template:STRUCTURE 2i5d

Contents

Crystal Structure of Human Inosine Triphosphate Pyrophosphatase

Template:ABSTRACT PUBMED 17077483

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]

About this Structure

2i5d is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • 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. ↑ 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
  2. ↑ 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
  3. ↑ 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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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