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5opn

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Revision as of 06:56, 16 October 2019

Crystal structure of R39Q cN-II mutant

Structural highlights

5opn 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.
Ligands:
Related:	5opl, 5opk, 5opm
Gene:	NT5C2, NT5B, NT5CP, PNT5 (HUMAN)
Activity:	5'-nucleotidase, with EC number 3.1.3.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[5NTC_HUMAN] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

[5NTC_HUMAN] May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides.

Publication Abstract from PubMed

Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418). Furthermore, analysis of hetero-oligomeric complexes combining wild-type (WT) and mutant subunits showed that the activation is transmitted from the mutated to the WT subunit. This intersubunit interaction forms structural basis of hyperactive NT5C2 in drug-resistant leukemia in which heterozygous NT5C2 mutation gave rise to hetero-tetramer mutant and WT proteins. This enabled us to define criteria to aid the prediction of NT5C2 drug resistance mutations in leukemia.

Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation.,Hnizda A, Fabry M, Moriyama T, Pachl P, Kugler M, Brinsa V, Ascher DB, Carroll WL, Novak P, Zaliova M, Trka J, Rezacova P, Yang JJ, Veverka V Leukemia. 2018 Jun;32(6):1393-1403. doi: 10.1038/s41375-018-0073-5. Epub 2018 Feb, 25. PMID:29535428^[2]

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

References

↑ Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014 Jan 31;343(6170):506-11. doi: 10.1126/science.1247363. PMID:24482476 doi:http://dx.doi.org/10.1126/science.1247363
↑ Hnizda A, Fabry M, Moriyama T, Pachl P, Kugler M, Brinsa V, Ascher DB, Carroll WL, Novak P, Zaliova M, Trka J, Rezacova P, Yang JJ, Veverka V. Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation. Leukemia. 2018 Jun;32(6):1393-1403. doi: 10.1038/s41375-018-0073-5. Epub 2018 Feb, 25. PMID:29535428 doi:http://dx.doi.org/10.1038/s41375-018-0073-5

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5opn"

@@ Line 1: / Line 1: @@
 ==Crystal structure of R39Q cN-II mutant==
-<StructureSection load='5opn' size='340' side='right' caption='[[5opn]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
+<StructureSection load='5opn' size='340' side='right'caption='[[5opn]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5opn]] is a 1 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=5OPN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OPN FirstGlance]. <br>
@@ Line 29: / Line 29: @@
 [[Category: 5'-nucleotidase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hnizda, A]]
 [[Category: Pachl, P]]

5opn

From Proteopedia

Revision as of 06:56, 16 October 2019

Crystal structure of R39Q cN-II mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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